MicroRNAs (miRNAs), which are a class of highly evolutionarily conserved non-coding RNAs, modulate gene expression and are regulated by specific genes. Several studies have shown that the expression of miRNAs is deregulated in Hepatitis C virus (HCV) & Hepatitis B virus (HBV) infection, liver cancer progression, tumor invasion and metastasis. There are a number of high-quality review articles relative to the general role of miRNA alterations in carcinogenesis and specific reviews dealing with the miRNA changes in hepatocellular carcinoma (HCC) and cholangio-carcinoma (CCA). Since primary liver cancer is predominantly comprised of HCC and intrahepatic cholangiocarcinoma (ICC), in the present review we specifically focus on recent advances of miRNAs related to tumorigenesis, invasion and metastasis of primary liver cancer, with special emphasis on their relationships to their target genes. HCV & HBV are major causes of liver disease, including acute and chronic hepatitis, liver cirrhosis, and HCC, while HCV infection is a risk factor for ICC. We also discuss the mi-RNA alterations involved in HCV & HBV infection. We briefly describe advances in molecular signaling of miRNAs in liver cancers and present insights into new therapeutic clues that target liver cancer.
KeywordsMicroRNAsHepatitis C virusHepatitis B VirusHepatocellular CarcinomaCholangiocarcinoma
A. Ichimura, Y. Ruike, K. Terasawa and G. Tsujimoto, “miRNAs and Regulation of Cell Signaling,” FEBS Journal, Vol. 278, No. 10, 2011, pp. 1610-1618. doi:10.1111/j.1742-4658.2011.08087.x
S. Djuranovic, A. Nahvi and R. Green, “A Parsimonious Model for Gene Regulation by miRNAs,” Science, Vol. 331, No. 6017, 2011, pp. 550-553. doi:10.1126/science.1191138
A. Aigner, “MicroRNAs (miRNAs) in Cancer Invasion and Metastasis: Therapeutic Approaches Based on Metastasis-Related miRNAs,” Journal of Molecular Medicine, Vol. 89, No. 5, 2011, pp. 445-457. doi:10.1007/s00109-010-0716-0
J. Brennecke, A. Stark, R. B. Russell and S. M. Cohen, “Principles of microRNA-Target Recognition,” Vol. 3, No. 3, 2005, p. e85. doi:10.1371/journal.pbio.0030085
W. Filipowicz, S. N. Bhattacharyya and N. Sonenberg, “Mechanisms of Post-Transcriptional Regulation by microRNAs: Are the Answers in Sight?” Nature Reviews Genetics, Vol. 9, No. 2, 2008, pp. 102-114. doi:10.1038/nrg2290
R. S. Pillai, “MicroRNA function: multiple mechanisms for a tiny RNA?” RNA Society, Vol. 11, No. 12, 2005, pp. 1753-1761. doi:10.1261/rna.2248605
T. Nissan and R. Parker, “Computational Analysis of miRNA-Mediated Repression of Translation: Implications for Models of Translation Initiation Inhibition,” RNA Society, Vol. 14, No. 8, 2008, pp. 1480-1491. doi:10.1261/rna.1072808
R. S. Pillai, S. N. Bhattacharyya and W. Filipowicz, “Repression of Protein Synthesis by miRNAs: How Many Mechanisms?” Trends in Cell Biology, Vol. 17, No. 3, 2007, pp. 118-126. doi:10.1016/j.tcb.2006.12.007
T. Du and P. D. Zamore, “Beginning to Understand microRNA Function,” Cell Research, Vol. 17, No. 8, 2007, pp. 661-663. doi:10.1038/cr.2007.67
A. Bashirullah, R. L. Cooperstock and H. D. Lipshitz, “Spatial and Temporal Control of RNA Stability,” Proceedings of the National Academy of Sciences, Vol. 98, No. 13, 2001, pp. 7025-7028. doi:10.1073/pnas.111145698
S. Kuersten and E. B. Goodwin, “The Power of the 3’ UTR: Translational Control and Development,” Nature Reviews Genetics, Vol. 4, No. 8, 2003, pp. 626-637. doi:10.1038/nrg1125
E. Li, T. H. Bestor and R. Jaenisch, “Targeted Mutation of the DNA Methyltransferase Gene Results in Embryonic Lethality,” Cell, Vol. 69, No. 6, 1992, pp. 915-926. doi:10.1016/0092-8674(92)90611-F
M. Okano, D. W. Bell, D. A. Haber and E. Li, “DNA Methyltransferases Dnmt3a and Dnmt3b are Essential for de novo Methylation and Mammalian Development,” Cell, Vol. 99, No. 3, 1999, pp. 247-257. doi:10.1016/S0092-8674(00)81656-6
R. T. Hay, “SUMO: A History of Modification,” Molecular Cell, Vol. 18, No. 1, 2005, pp. 1-12. doi:10.1016/j.molcel.2005.03.012
M. Fabbri and G. A. Calin, “Epigenetics and miRNAs in Human Cancer,” Advance in Genetics, Vol. 70, 2010, pp. 87-99. doi:10.1016/B978-0-12-380866-0.60004-6
M. Fabbri, R. Garzon, A. Cimmino, Z. Liu, N. Zanesi, E. Callegari, S. Liu, H. Alder, S. Costinean, C. Fernandez-Cymering, et al., “MicroRNA-29 Family Reverts Aberrant Methylation in Lung Cancer by Targeting DNA Methyltransferases 3A and 3B,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 40, 2007, pp. 15805-15810. doi:10.1073/pnas.0707628104
L. Sinkkonen, T. Hugenschmidt, P. Berninger, D. Gaidatzis, F. Mohn, C. G. Artus-Revel, M. Zavolan, P. Svoboda and W. Filipowicz, “MicroRNAs Control de novo DNA Methylation through Regulation of Transcriptional Repressors in Mouse Embryonic Stem Cells,” Nature Structural & Molecular Biology, Vol. 15, No. 3, 2008, pp. 259-267. doi:10.1038/nsmb.1391
A. M. Duursma, M. Kedde, M. Schrier, C. le Sage, R. Agami, “miR-148 targets human DNMT3b protein coding region,” RNA Society, Vol. 14, No. 5, 2008, pp. 872-877. doi:10.1261/rna.972008
U. Lehmann, B. Hasemeier, M. Christgen, M. Muller, D. Romermann, F. Langer and H. Kreipe, “Epigenetic Inactivation of microRNA Gene Hsa-mir-9-1 in Human Breast Cancer,” The Journal of Pathology, Vol. 214, No. 1, 2008, pp.17-24. doi:10.1002/path.2251
A. Lujambio, G. A. Calin, A. Villanueva, S. Ropero, M. Sanchez-Cespedes, D. Blanco, L. M. Montuenga, S. Rossi, M. S. Nicoloso, W. J. Faller, et al., “A microRNA DNA Methylation Signature for Human Cancer Metastasis,” Proceedings of the National Academy of Sciences USA, Vol. 105, No. 36, 2008, pp. 13556-13561. doi:10.1073/pnas.0803055105
C. Braconi, N. Huang and T. Patel, “MicroRNA-Dependent Regulation of DNA Methyltransferase-1 and Tumor Suppressor Gene Expression by Interleukin-6 in Human Malignant Cholangiocytes,” Hepatology, Vol. 51, No. 3, 2010, pp. 881-890.
J. F. Chen, E. M. Mandel, J. M. Thomson, Q. Wu, T. E. Callis, S. M. Hammond, F. L. Conlon and D. Z. Wang, “The Role of microRNA-1 and microRNA-133 in Skeletal Muscle Proliferation and Differentiation,” Nature Genetics, Vol. 38, No. 2, 2006, pp. 228-233. doi:10.1038/ng1725
L. Tuddenham, G. Wheeler, S. Ntounia-Fousara, J. Waters, M. K. Hajihosseini, I. Clark and T. Dalmay, “The Cartilage Specific microRNA-140 Targets Histone Deacetylase 4 in Mouse Cells,” FEBS Letters, Vol. 580, No. 17, 2006, pp. 4214-4217. doi:10.1016/j.febslet.2006.06.080
E. J. Noonan, R. F. Place, D. Pookot, S. Basak, J. M. Whitson, H. Hirata, C. Giardina and R. Dahiya, “miR- 449a Targets HDAC-1 and Induces Growth Arrest in Prostate Cancer,” Oncogene, Vol. 28, No. 14, 2009, pp. 1714-1724. doi:10.1038/onc.2009.19
J. M. Friedman, G. Liang, C. C. Liu, E. M. Wolff, Y. C. Tsai, W. Ye, X. Zhou and P. A. Jones, “The Putative Tumor Suppressor microRNA-101 Modulates the Cancer Epigenome by Repressing the Polycomb Group Protein EZH2,” Cancer Research, Vol. 69, No. 6, 2009, pp. 2623-2629. doi:10.1158/0008-5472.CAN-08-3114
S. Varambally, Q. Cao, R. S. Mani, S. Shankar, X. Wang, B. Ateeq, B. Laxman, X. Cao, X. Jing, K. Ramnarayanan, et al., “Genomic Loss of microRNA-101 Leads to Overexpression of Histone Methyltransferase EZH2 in Cancer,” Science, Vol. 322, No. 5908, 2008, pp. 1695-1699. doi:10.1126/science.1165395
V. Maselli, D. Di Bernardo and S. Banfi, “CoGemiR: A Comparative Genomics microRNA Database,” BMC Genomics, Vol. 9, No. 1, 2008, p. 457. doi:10.1186/1471-2164-9-457
J. H. Yang, P. Shao, H. Zhou, Y. Q. Chen, L. H. Qu, “DeepBase: A Database for Deeply Annotating and Mining Deep Sequencing Data,” Nucleic Acids Research, Vol. 38, No. 1, 2010, pp. D123-D130. doi:10.1093/nar/gkp943
M. Maragkakis, M. Reczko, V. A. Simossis, P. Alexiou, G. L. Papadopoulos, T. Dalamagas, G. Giannopoulos, G. Goumas, E. Koukis, K. Kourtis, et al., “DIANA-microT Web Server: Elucidating microRNA Functions through Target Prediction,” Nucleic Acids Research, Vol. 37, No. 2, 2009, pp. W273-W276. doi:10.1093/nar/gkp292
F. Xiao, Z. Zuo, G. Cai, S. Kang, X. Gao and T. Li, “miRecords: An Integrated Resource for microRNA- Target Interactions,” Nucleic Acids Research, Vol. 37, No. 1, 2009, pp. D105-D110.doi:10.1093/nar/gkn851
K. C. Miranda, T. Huynh, Y. Tay, Y. S. Ang, W. L. Tam, A. M. Thomson, B. Lim and I. Rigoutsos, “A Pattern-Based Method for the Identification of MicroRNA Binding Sites and Their Corresponding Heteroduplexes,” Cell, Vol. 126, No. 6, 2006, pp. 1203-12017. doi:10.1016/j.cell.2006.07.031
M. Kertesz, N. Iovino, U. Unnerstall, U. Gaul and E. Segal, “The Role of Site Accessibility in microRNA Target Recognition,” Nat Genet, Vol. 39, No. 10, 2007, pp. 1278-1284. doi:10.1038/ng2135
D. Betel, M. Wilson, A. Gabow, D. S. Marks and C. Sander, “The microRNA.org resource: targets and expression,” Nucleic Acids Research, Vol. 36, No. 1, 2008, pp. D149-D153. doi:10.1093/nar/gkm995
J. H. Yang, J. H. Li, P. Shao, H. Zhou, Y. Q. Chen, L. H. Qu, “StarBase: A Database for Exploring microRNA-mRNA Interaction Maps from Argonaute CLIP-Seq and Degradome-Seq Data,” Nucleic Acids Research, Vol. 39, No. 1, 2011, pp. D202-D209. doi:10.1093/nar/gkq1056
A. Stark, J. Brennecke, R. B. Russell and S. M. Cohen, “Identification of Drosophila MicroRNA targets, ” PLOS Biology, Vol. 1, No. 3, 2003, p. E60. doi:10.1371/journal.pbio.0000060
N. Rajewsky and N. D. Socci, “Computational Identification of microRNA Targets,” Developmental Biology, Vol. 267, No. 2, 2004, pp. 529-535. doi:10.1016/j.ydbio.2003.12.003
B. John, A. J. Enright, A. Aravin, T. Tuschl, C. Sander, D. S. Marks, “Human MicroRNA targets,” PLOS Biology, Vol. 2, No. 11, 2004, p. e363. doi:10.1371/journal.pbio.0020363
A. J. Enright, B. John, U. Gaul, T. Tuschl, C. Sander and D. S. Marks, “MicroRNA Targets in Drosophila,” Genome Biology, Vol. 5, No. 1, 2003, p. R1. doi:10.1186/gb-2003-5-1-r1
B. P. Lewis, C. B. Burge and D. P. Bartel, “Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are microRNA Targets,” Cell, Vol. 120, No. 1, 2005, pp. 15-20. doi:10.1016/j.cell.2004.12.035
M. Kiriakidou, P. T. Nelson, A. Kouranov, P. Fitziev, C. Bouyioukos, Z. Mourelatos and A. Hatzigeorgiou, “A Combined Computational-Experimental Approach Predicts Human microRNA Targets,” Genes & Development, Vol. 18, No. 10, 2004, pp. 1165-1178. doi:10.1101/gad.1184704
A. Krek, D. Grün, M. N. Poy, R. Wolf, L. Rosenberg, E. J. Epstein, P. MacMenamin, I. da Piedade, K. C. Gunsalus, M. Stoffel and N. Rajewsky, “Combinatorial microRNA Target Predictions,” Nature Genetics, Vol. 37, No. 5, 2005, pp. 495-500. doi:10.1038/ng1536
M. Rehmsmeier, P. Steffen, M. Hochsmann and R. Giegerich, “Fast and Effective Prediction of microRNA/ Target Duplexes,” RNA Society, Vol. 10, No. 10, 2004, pp. 1507-1517. doi:10.1261/rna.5248604
J. C. Huang, T. Babak, T. W. Corson, G. Chua, S. Khan, B. L. Gallie, T. R. Hughes, B. J. Blencowe, B. J. Frey, Q. D. Morris, “Using Expression Profiling Data to Identify Human microRNA Targets,” Nature Methods, Vol. 4, No. 12, 2007, pp. 1045-1049. doi:10.1038/nmeth1130
X. Wang and I. M. El Naqa, “Prediction of Both Conserved and Nonconserved microRNA Targets in Animals,” Bioinformatics, Vol. 24, No. 3, 2008, pp. 325-332. doi:10.1093/bioinformatics/btm595
P. Sethupathy, M. Megraw and A. G. Hatzigeorgiou, “A Guide through Present Computational Approaches for the Identification of Mammalian microRNA Targets,” Nature Methods, Vol. 3, No. 11, 2006, pp. 881-886. doi:10.1038/nmeth954
G. Tzur, A. Israel, A. Levy, H. Benjamin, E. Meiri, Y. Shufaro, K. Meir, E. Khvalevsky, Y. Spector, N. Rojansky, et al., “Comprehensive Gene and microRNA Expression Profiling Reveals a Role for microRNAs in Human Liver Development,” PLoS One, Vol. 4, No. 10, 2009, p. e7511. doi:10.1371/journal.pone.0007511
K. P. Porkka, M. J. Pfeiffer, K. K. Waltering, R. L. Vessella, T. L. Tammela and T. Visakorpi, “MicroRNA Expression Profiling in Prostate Cancer,” Cancer Research, Vol. 67, No. 13, 2007, pp. 6130-6135. doi:10.1158/0008-5472.CAN-07-0533
F. Petrocca, A. Vecchione and C. M. Croce, “Emerging Role of miR-106b-25/miR-17-92 Clusters in the Control of Transforming Growth Factor Beta Signaling,” Cancer Research, Vol. 68, No. 20, 2008, pp. 8191-8194. doi:10.1158/0008-5472.CAN-08-1768
C. M. Croce, “Causes and Consequences of microRNA Dysregulation in Cancer,” Nature Reviews Genetics, Vol. 10, No. 10, 2009, pp. 704-714. doi:10.1038/nrg2634
N. Li, C. Wei, A. F. Olena and J. G. Patton, “Regulation of Endoderm Formation and Left-Right Asymmetry by miR-92 during Early Zebrafish Development,” Development, Vol. 138, No. 9, 2011, pp. 1817-1826. doi:10.1242/dev.056697
Y. S. Lee and A. Dutta, “The Tumor Suppressor mi-croRNA Let-7 Represses the HMGA2 Oncogene,” Genes & Development, Vol. 21, No. 9, 2007, pp. 1025-1030. doi:10.1101/gad.1540407
B. Boyerinas, S. M. Park, N. Shomron, M. M. Hedegaard, J. Vinther, J. S. Andersen, C. Feig, J. Xu, C. B. Burge and M. E. Peter, “Identification of Let-7-Regulated Oncofetal Genes,” Cancer Research, Vol. 68, No. 8, 2008, pp. 2587-2591. doi:10.1158/0008-5472.CAN-08-0264
H. Xu, J. H. He, Z. D. Xiao, Q. Q. Zhang, Y. Q. Chen, H. Zhou and L. H. Qu, “Liver-Enriched Transcription Factors Regulate microRNA-122 that Targets CUTL1 during Liver Development,” Hepatology, Vol. 52, No. 4, 2010, pp. 1431-1442. doi:10.1002/hep.23818
J. Hou, L. Lin, W. Zhou, Z. Wang, G. Ding, Q. Dong, L. Qin, X. Wu, Y. Zheng, Y. Yang, et al., “Identification of miRNomes in Human Liver and Hepatocellular Carcinoma Reveals miR-199a/b-3p as Therapeutic Target for Hepatocellular Carcinoma,” Cancer Cell, Vol. 19, No. 2, 2011, pp. 232-243. doi:10.1016/j.ccr.2011.01.001
N. Raschzok, W. Werner, H. Sallmon, N. Billecke, C. Dame, P. Neuhaus and I. M. Sauer, “Temporal Expression Profiles Indicate a Primary Function for microRNA during the Peak of DNA Replication after Rat Partial Hepatectomy,” American Journal of Physiology—Regulatory, Integrative and Comparative Physiology, Vol. 300, No. 6, 2011, pp. R363-R372. doi:10.1152/ajpregu.00632.2010
D. Liu, J. Fan, W. Zeng, Y. Zhou, S. Ingvarsson and H. Chen, “Quantitative Analysis of miRNA Expression in Several Developmental Stages of Human Livers,” Hepatology Research, Vol. 40, No. 8, 2010, pp. 813-822. doi:10.1111/j.1872-034X.2010.00683.x
S. S?ber, M. Laan and T. Annilo, “MicroRNAs miR-124 and miR-135a are Potential Regulators of the Mineralocorticoid Receptor Gene (NR3C2) Expression,” Biochemical and Biophysical Research Communications, Vol. 391, No. 1, 2010, pp. 727-732. doi:10.1016/j.bbrc.2009.11.128
P. P. Medina and F. J. Slack, “MicroRNAs and Cancer: An Overview,” Cell Cycle, Vol. 7, No. 16, 2008, pp. 2485-2492. doi:10.4161/cc.7.16.6453
L. Agnelli, L. Mosca, S. Fabris, M. Lionetti, A. Andronache, I. Kwee, K. Todoerti, D. Verdelli, C. Battaglia, F. Bertoni, et al., “A SNP Microarray and FISH-Based Procedure to Detect Allelic Imbalances in Multiple Myeloma: An Integrated Genomics Approach Reveals a Wide Gene Dosage Effect,” Genes Chromosomes Cancer, Vol. 48, No. 7, 2009, pp. 603-614. doi:10.1002/gcc.20668
K. Sakurai, C. Furukawa, T. Haraguchi, K. Inada, K. Shiogama, T. Tagawa, S. Fujita, Y. Ueno, A. Ogata, M. Ito, Y. Tsutsumi and H. Iba, “MicroRNAs miR-199a-5p and -3p Target the Brm Subunit of SWI/SNF to Generate a Double-Negative Feedback Loop in a Variety of Human Cancers,” Cancer Research, Vol. 71, 2011, pp. 1680-1689. doi:10.1158/0008-5472.CAN-10-2345
A. A. Dar, S. Majid, D. de Semir, M. Nosrati, V. Bez-rookove and M. Kashani-Sabet, “miR-205 Suppresses Melanoma Cell Proliferation and Induces Senescence via Regulation of E2F1,” The Journal of Biological Chemistry, Vol. 286, No. 19, 2011, pp. 16606-16614. doi:10.1074/jbc.M111.227611
B. K. Dey, J. Gagan and A. Dutta, “miR-206 and -486 Induce Myoblast Differentiation by Downregulating Pax7,” Molecular and Cellular Biology, Vol. 31, 2011, pp. 203- 214. doi:10.1128/MCB.01009-10
W. P. Tsang and T. T. Kwok, “The miR-18a microRNA Functions as a Potential Tumor Suppressor by Targeting on K-Ras,” Carcinogenesis, Vol. 30, 2009, pp. 953-959. doi:10.1093/carcin/bgp094
T. Ohgawara, S. Kubota, H. Kawaki, S. Kondo, T. Eguchi, N. Kurio, E. Aoyama, A. Sasaki and M. Takigawa, “Regulation of Chondrocytic Phenotype by Micro RNA 18a: Involvement of Ccn2/Ctgf as a Major Target Gene,” FEBS Letters, Vol. 583, 2009, pp. 1006-1010. doi:10.1016/j.febslet.2009.02.025
J. B. Patel, H. N. Appaiah, R. M. Burnett, P. Bhat-Nakshatri, G. Wang, R. Mehta, S. Badve, M. J. Thomson, S. Hammond, P. Steeg, Y. Liu and H. Nakshatri, “Control of EVI-1 Oncogene Expression in Metastatic Breast Cancer Cells through microRNA miR-22,” Oncogene, Vol. 30, 2011, pp. 1290-1301. doi:10.1038/onc.2010.510
W. Liu, O. Zabirnyk, H. Wang, Y. H. Shiao, M. L. Nickerson, S. Khalil, L. M. Anderson, A. O. Perantoni, J. M. Phang, “miR-23b Targets Proline Oxidase, a Novel Tumor Suppressor Protein in Renal Cancer,” Oncogene, Vol. 29, No. 35, 2010, pp. 4914-4924. doi:10.1038/onc.2010.237
A. Fort, C. Borel, E. Migliavacca, S. E. Antonarakis, R. J. Fish and M. Neerman-Arbez, “Regulation of Fibrinogen Production by microRNAs,” Blood, Vol. 116, No. 14, 2010, pp. 2608-2615. doi:10.1182/blood-2010-02-268011
Z. L. Chen, X. H. Zhao, J. W. Wang, B. Z. Li, Z. Wang, J. Sun, F. W. Tan, D. P. Ding, X. H. Xu, F. Zhou, et al., “MicroRNA-92a Promotes Lymph Node Metastasis of Human Esophageal Squamous Cell Carcinoma via E-Cadherin,” The Journal of Biological Chemistry, Vol. 286, No. 12, 2011, pp. 10725-10734. doi:10.1074/jbc.M110.165654
M. R. Benakanakere, Q. Li, M. A. Eskan, A. V. Singh, J. Zhao, J. C. Galicia, P. Stathopoulou, T. B. Knudsen, D. F. Kinane, “Modulation of TLR2 Protein Expression by miR-105 in Human Oral Keratinocytes,” The Journal of Biological Chemistry, Vol. 284, No. 34, 2009, pp. 23107- 23115. doi:10.1074/jbc.M109.013862
S. A. Georges, M. C. Biery, S. Y. Kim, J. M. Schelter, J. Guo, A. N. Chang, A. L. Jackson, M. O. Carleton, P. S. Linsley, M. A. Cleary, et al., “Coordinated Regulation of Cell Cycle Transcripts by p53-Inducible microRNAs, miR-192 and miR-215,” Cancer Research, Vol. 68, No. 24, 2008, pp. 10105-10112. doi:10.1158/0008-5472.CAN-08-1846
Y. Murakami, T. Yasuda, K. Saigo, T. Urashima, H. Toyoda, T. Okanoue and K. Shimotohno, “Comprehensive Analysis of microRNA Expression Patterns in Hepato-cellular Carcinomaand Non-Tumorous Tissues,” Oncogene, Vol. 25, No. 17, 2006, pp. 2537-2545. doi:10.1038/sj.onc.1209283
Y. S. Huang, Y. Dai, X. F. Yu, S. Y. Bao, Y. B. Yin, M. Tang and C. X. Hu, “Microarray Analysis of microRNA Expression in hepatocellular Carcinoma and Non-Tumorous Tissues without Viral Hepatitis,” Journal of Gas-troenterology and Hepatology, Vol. 23, No. 1, 2008, pp. 87-94. doi:10.1111/j.1440-1746.2007.05223.x
M. Furuta, K. I. Kozaki, S. Tanaka, S. Arii, I. Imoto and J. Inazawa, “MiR-124 and miR-203 are Epigenetically Silenced Tumor-Suppressive microRNAs in Hepatocellular Carcinoma,” Carcinogenesis, Vol. 31, No. 5, 2010, pp. 766-776. doi:10.1093/carcin/bgp250
G. E. Chung, J. H. Yoon, S. J. Myung, J. H. Lee, S. H. Lee, S. M. Lee, S. J. Kim, S. Y. Hwang, H. S. Lee and C. Y. Kim, “High Expression of microRNA-15b Predicts a Low Risk of Tumor Recurrence Following Curative Resection of Hepatocellular Carcinoma,” Oncology Reports, Vol. 23, No. 1, 2010, pp. 113-119.
I. Barshack, E. Meiri, S. Rosenwald, D. Lebanony, M. Bronfeld, S. Aviel Ronen, K. Rosenblatt, S. Polak- Charcon, I. Leizerman, M. Ezagouri, et al., “Differential Diagnosis of Hepatocellular Carcinoma from Metastatic Tumors in the Liver Using microRNA Expression,” The International Journal of Biochemistry & Cell Biology, Vol. 42, No. 8, 2010, pp. 1355-1362. doi:10.1016/j.biocel.2009.02.021
M. Shigoka, A. Tsuchida, T. Matsudo, Y. Nagakawa, H. Saito, Y. Suzuki, T. Aoki, Y. Murakami, H. Toyoda, T. Kumada, et al., “Deregulation of miR-92a Expression is Implicated in Hepatocellular Carcinoma Development,” Pathology International, Vol. 60, No. 5, 2010, pp. 351- 357. doi:10.1111/j.1440-1827.2010.02526.x
Q. W. Wong, A. K. Ching, A. W. Chan, K. W. Choy, K. F. To, P. B. Lai and N. Wong, “MiR-222 Overexpression Confers Cell Migratory Advantages in Hepatocellular Carcinoma through Enhancing AKT Signaling,” Clinical Cancer Research, Vol. 16, No. 3, 2010, pp. 867-875. doi:10.1158/1078-0432.CCR-09-1840
L. Gramantieri, F. Fornari, E. Callegari, S. Sabbioni, G. Lanza, C. M. Croce, L. Bolondi and M. Negrini, “MicroRNA Involvement in Hepatocellular Carcinoma,” Journal of Cellular and Molecular Medicine, Vol. 12, No. 6, 2008, pp. 2189-2204. doi:10.1111/j.1582-4934.2008.00533.x
Y. Wang, A. T. Lee, J. Z. Ma, J. Wang, J. Ren, Y. Yang, E. Tantoso, K. B. Li, L. L. Ooi, P. Tan, et al., “Profiling microRNA Expression in Hepatocellular Carcinoma Reveals microRNA-224 Up-Regulation and Apoptosis Inhibitor-5 as a microRNA-224-Specific Target,” The Journal of Biological Chemistry, Vol. 283, No. 19, 2008, pp. 13205-13215. doi:10.1074/jbc.M707629200
F. Fornari, M. Milazzo, P. Chieco, M. Negrini, G. A. Calin, G. L. Grazi, D. Pollutri, C. M. Croce, L. Bolondi and L. Gramantieri, “MiR-199a-3p Regulates mTOR and c-Met to Influence the Doxorubicin Sensitivity of Human Hepatocarcinoma Cells,” Cancer Research, Vol. 70, No. 12, 2010, pp. 5184-5193. doi:10.1158/0008-5472.CAN-10-0145
S. Toffanin, Y. Hoshida, A. Lachenmayer, A. Villanueva, L. Cabellos, B. Minguez, R. Savic, S. C. Ward, S. Thung, D. Y. Chiang, et al., “MicroRNA-Based Classification of Hepatocellular Carcinoma and Oncogenic Role of miR-517a,” Gastroenterology, Vol. 140, No. 5, 2011, pp. 1618-1628. doi:10.1053/j.gastro.2011.02.009
J. Kota, R. R. Chivukula, K. A. O’Donnell, E. A. Wentzel, C. L. Montgomery, H. W. Hwang, T. C. Chang, P. Vivekanandan, M. Torbenson, K. R. Clark, et al., “Therapeutic microRNA Delivery Suppresses Tumorigenesis in a Murine Liver Cancer Model,” Cell, Vol. 137, 2009, No. 1005-1017. doi:10.1016/j.cell.2009.04.021
L. Gramantieri, M. Ferracin, F. Fornari, A. Veronese, S. Sabbioni, C. G. Liu, G. A. Calin, C. Giovannini, E. Ferrazzi, G. L. Grazi, et al., “Cyclin G1 is a Target of miR-122a, a microRNA Frequently Down-Regulated in Human Hepatocellular Carcinoma,” Cancer Research, Vol. 67, No. 13, 2007, pp. 6092-6099. doi:10.1158/0008-5472.CAN-06-4607
T. Xu, Y. Zhu, Y. Xiong, Y. Y. Ge, J. P. Yun and S. M. Zhuang, “MicroRNA-195 Suppresses Tumorigenicity and Regulates G1/S Transition of Human Hepatocellular Carcinoma Cells,” Hepatology, Vol. 50, No. 1, 2009, pp. 113-121. doi:10.1002/hep.22919
F. F. Lan, H. Wang, Y. C. Chen, C. Y. Chan, S. S. Ng, K. Li, D. Xie, M. L. He, M. C. Lin and H. F. Kung, “Hsa-let-7g Inhibits Proliferation of Hepatocellular Carcinoma Cells by Down-Regulation of c-Myc and Up-Regulation of p16(INK4A),” International Journal of Cancer, Vol. 128, No. 2, 2010, pp. 319-331. doi:10.1002/ijc.25336
C. le Sage, R. Nagel, D. A. Egan, M. Schrier, E. Mesman, A. Mangiola, C. Anile, G. Maira, N. Mercatelli, S. A. Ciafre, et al., “Regulation of the p27(Kip1) Tumor Suppressor by miR-221 and miR-222 Promotes Cancer Cell Proliferation,” The EMBO Journal, Vol. 26, No. 15, 2007, pp. 3699-3708. doi:10.1038/sj.emboj.7601790
F. Fornari, L. Gramantieri, M. Ferracin, A. Veronese, S. Sabbioni, G. A. Calin, G. L. Grazi, C. Giovannini, C. M. Croce, L. Bolondi, et al., “MiR-221 Controls CDKN1C/ p57 and CDKN1B/p27 Expression in Human Hepatocellular Carcinoma,” Oncogene, Vol. 27, 2008, pp. 5651-5661. doi:10.1038/onc.2008.178
I. Ivanovska, A. S. Ball, R. L. Diaz, J. F. Magnus, M. Kibukawa, J. M. Schelter, S. V. Kobayashi, L. Lim, J. Burchard, A. L. Jackson, et al., “MicroRNAs in the miR-106b Family Regulate p21/CDKN1A and Promote Cell Cycle Progression,” Molecular and Cellular Biology, Vol. 28, No. 7, 2008, pp. 2167-2174. doi:10.1128/MCB.01977-07
N. Wu, X. Liu, X. Xu, X. Fan, M. Liu, X. Li, Q. Zhong and H. Tang, “MiR-373, a Novel Regulator of PPP6C, Functions as an Oncogene in Hepatocellular Carcinoma,” FEBS Journal, Vol. 278, 2011, pp. 2044-2054. doi:10.1111/j.1742-4658.2011.08120.x
C. J. Lin, H. Y. Gong, H. C. Tseng, W. L. Wang and J. L. Wu, “miR-122 Targets an Anti-Apoptotic Gene, Bcl-w, in Human Hepatocellular Carcinoma Cell Lines,” Biochemical and Biophysical Research Communications, Vol. 375, No. 3, 2008, pp. 315-320. doi:10.1016/j.bbrc.2008.07.154
P. Pineau, S. Volinia, K. McJunkin, A. Marchio, C. Bat-tiston, B. Terris, V. Mazzaferro, S. W. Lowe, C. M. Croce and A. Dejean, “miR-221 Overexpression Contributes to Liver Tumorigenesis,” Proceedings of the National Academy of Sciences USA, Vol. 107, No. 1, 2010, pp. 264-269. doi:10.1073/pnas.0907904107
S. Bai, M. W. Nasser, B. Wang, S. H. Hsu, J. Datta, H. Kutay, A. Yadav, G. Nuovo, P. Kumar and K. Ghoshal, “MicroRNA-122 Inhibits Tumorigenic Properties of Hepatocellular Carcinoma Cells and Sensitizes These Cells to Sorafenib,” The Journal of Biological Chemistry, Vol. 284, No. 46, 2009, pp. 32015-32027. doi:10.1074/jbc.M109.016774
C. Coulouarn, V. M. Factor, J. B. Andersen, M. E. Durkin and S. S. Thorgeirsson, “Loss of miR-122 Expression in Liver Cancer Correlates with Suppression of the Hepatic Phenotype and Gain of Metastatic Properties,” Oncogene, Vol. 28, No. 40, 2009, pp. 3526-3536. doi:10.1038/onc.2009.211
F. Fornari, L. Gramantieri, C. Giovannini, A. Veronese, M. Ferracin, S. Sabbioni, G. A. Calin, G. L. Grazi, C. M. Croce, S. Tavolari, et al., “MiR-122/cyclin G1 Interaction Modulates p53 Activity and Affects Doxorubicin Sensitivity of Human Hepatocarcinoma Cells,” Cancer Research, Vol. 69, No. 14, 2009, pp. 5761-5767. doi:10.1158/0008-5472.CAN-08-4797
W. C. Tsai, P. W. Hsu, T. C. Lai, G. Y. Chau, C. W. Lin, C. M. Chen, C. D. Lin, Y. L. Liao, J. L. Wang, Y. P. Chau, et al., “MicroRNA-122, a Tumor Suppressor Microrna that Regulates Intrahepatic Metastasis of Hepato-cellular Carcinoma,” Hepatology, Vol. 49, No. 5, 2009, pp. 1571-1582. doi:10.1002/hep.22806
L. Ma, J. Liu, J. Shen, L. Liu, J. Wu, W. Li, J. Luo, Q. Chen and C. Qian, “Expression of miR-122 Mediated by Adenoviral Vector Induces Apoptosis and Cell Cycle Arrest of Cancer Cells,” Cancer Biology and Therapy, Vol. 9, No. 7, 2010, pp. 554-561. doi:10.4161/cbt.9.7.11267
R. Zhang, L. Wang, G. R. Yu, X. Zhang, L. B. Yao, A. G. Yang, “MicroRNA-122 Might be a Double-Edged Sword in Hepatocellular Carcinoma,” Hepatology, Vol. 50, 2009, pp. 1322-1323. doi:10.1002/hep.23108
J. Ji, L. Zhao, A. Budhu, M. Forgues, H. L. Jia, L. X. Qin, Q. H. Ye, J. Yu, X. Shi, Z. Y. Tang, et al., “Let-7g Targets Collagen Type I Alpha2 and Inhibits Cell Migration in Hepatocellular Carcinoma,” Journal of Hepatology, Vol. 52, No. 5, 2010, pp. 690-697. doi:10.1016/j.jhep.2009.12.025
S. Shimizu, T. Takehara, H. Hikita, T. Kodama, T. Miyagi, A. Hosui, T. Tatsumi, H. Ishida, T. Noda, H. Nagano, et al., “The Let-7 Family of microRNAs Inhibits Bcl-xL Expression and Potentiates Sorafenib-Induced Apoptosis in Human Hepatocellular Carcinoma,” Journal of Hepatology, Vol. 52, No. 6, 2010, pp. 698-704. doi:10.1016/j.jhep.2009.12.024
M. Garofalo, G. Di Leva, G. Romano, G. Nuovo, S. S. Suh, A. Ngankeu, C. Taccioli, F. Pichiorri, H. Alder, P. Secchiero, et al., “miR-221 & 222 Regulate TRAIL Resistance and Enhance Tumorigenicity through PTEN and TIMP3 Downregulation,” Cancer Cell, Vol. 16, 2009, No. 498-509. doi:10.1016/j.ccr.2009.10.014
L. Gramantieri, F. Fornari, M. Ferracin, A. Veronese, S. Sabbioni, G. A. Calin, G. L. Grazi, C. M. Croce, L. Bolondi and M. Negrini, “MicroRNA-221 Targets Bmf in Hepatocellular Carcinoma and Correlates with Tumor Multifocality,” Clinical Cancer Research, Vol. 15, No. 18, 2009, pp. 5073-5081. doi:10.1158/1078-0432.CCR-09-0092
Y. Li, W. Tan, T. W. Neo, M. O. Aung, S. Wasser, S. G. Lim, T. M. Tan, “Role of the miR-106b-25 microRNA Cluster in Hepatocellular Carcinoma,” Cancer Science, Vol. 100, 2009, pp. 1234-1242. doi:10.1111/j.1349-7006.2009.01164.x
I. Ivanovska, A. S. Ball, R. L. Diaz, J. F. Magnus, M. Kibukawa, J. M. Schelter, S. V. Kobayashi, L. Lim, J. Burchard, A. L. Jackson, et al., “MicroRNAs in the miR-106b Family Regulate p21/CDKN1A and Promote Cell Cycle Progression,” Molecular and Cellular Biology, Vol. 28, No. 7, 2008, pp. 2167-2174. doi:10.1128/MCB.01977-07
F. Meng, R. Henson, H. Wehbe-Janek, K. Ghoshal, S. T. Jacob and T. Patel, “MicroRNA-21 Regulates Expression of the PTEN Tumor Suppressor Gene in Human Hepato-cellular Cancer,” Gastroenterology, Vol. 133, No. 2, 2007, pp. 647-658. doi:10.1053/j.gastro.2007.05.022
Q. W. Wong, R. W. Lung, P. T. Law, P. B. Lai, K. Y. Chan, K. F. To and N. Wong, “MicroRNA-223 is Commonly Repressed in Hepatocellular Carcinoma and Potentiates Expression of Stathmin1,” Gastroenterology, Vol. 135, No. 1, 2008, pp. 257-269. doi:10.1053/j.gastro.2008.04.003
L. Wu, C. Cai, X. Wang, M. Liu, X. Li and H. Tang, “MicroRNA-142-3p, a New Regulator of RAC1, Suppresses the Migration and Invasion of Hepatocellular Carcinoma Cells,” FEBS Letters, Vol. 585, No. 9, 2011, pp. 1322-1330. doi:10.1016/j.febslet.2011.03.067
J. Ding, S. Huang, S. Wu, Y. Zhao, L. Liang, M. Yan, C. Ge, J. Yao, T. Chen, D. Wan, et al., “Gain of miR-151 on Chromosome 8q24.3 Facilitates Tumour Cell Migration and Spreading through Downregulating RhoGDIA,” Nature Cell Biology, Vol. 12, No. 4, 2010, pp. 390-399. doi:10.1038/ncb2039
B. Wang, S. H. Hsu, S. Majumder, H. Kutay, W. Huang, S. T. Jacob and K. Ghoshal, “TGFbeta-Mediated Upregulation of Hepatic miR-181b Promotes Hepatocarcinogenesis by Targeting TIMP3,” Oncogene, Vol. 29, No. 12, 2010, pp. 1787-1797. doi:10.1038/onc.2009.468
J. Yao, L. Liang, S. Huang, J. Ding, N. Tan, Y. Zhao, M. Yan, C. Ge, Z. Zhang, T. Chen, et al., “MicroRNA-30d Promotes Tumor Invasion and Metastasis by Targeting Galphai2 in Hepatocellular Carcinoma,” Hepatology, Vol. 51, No. 3, 2010, pp. 846-856.
D. R. Hurst, M. D. Edmonds and D. R. Welch, “Metastamir: The Field of Metastasis-Regulatory microRNA is Spreading,” Cancer Research, Vol. 69, No. 19, 2009, pp. 7495-7498. doi:10.1158/0008-5472.CAN-09-2111
M. Garofalo, G. Di Leva, G. Romano, G. Nuovo, S. S. Suh, A. Ngankeu, C. Taccioli, F. Pichiorri, H. Alder, P. Secchiero, et al., “miR-221 & 222 Regulate TRAIL Resistance and Enhance Tumorigenicity through PTEN and TIMP3 Downregulation,” Cancer Cell, Vol. 16, 2009, pp. 498-509. doi:10.1016/j.ccr.2009.10.014
D. M. Dykxhoorn, “MicroRNAs and Metastasis: Little RNAs Go a Long Way,” Cancer Research, Vol. 70, No. 16, 2010, pp. 6401-6406. doi:10.1158/0008-5472.CAN-10-1346
H. Yang, T. W. Li, J. Peng, X. Tang, K. S. Ko, M. Xia, M. A. Aller, “A Mouse Model of Cholestasis-Associated Cholangiocarcinoma and Transcription Factors Involved in Progression,” Gastroenterology, Vol. 141, No. 1, 2011, pp. 378-388. doi:10.1053/j.gastro.2011.03.044
L. Chen, H. X. Yan, W. Yang, L. Hu, L. X. Yu, Q. Liu, L. Li, D. D. Huang, J. Ding, F. Shen, et al., “The Role of microRNA Expression Pattern in Human Intrahepatic Cholangiocarcinoma,” Journal of Hepatology, Vol. 50, No. 2, 2009, pp. 358-369. doi:10.1016/j.jhep.2008.09.015
Y. Kawahigashi, T. Mishima, Y. Mizuguchi, Y. Arima, S. Yokomuro, T. Kanda, O. Ishibashi, H. Yoshida, T. Tajiri and T. Takizawa, “MicroRNA Profiling of Human Intrahepatic Cholangiocarcinoma Cell Lines Reveals Biliary Epithelial Cell-Specific microRNAs,” Journal of Nippon Medical School, Vol. 76, No. 4, 2009, pp. 188-197. doi:10.1272/jnms.76.188
C. Braconi, N. Huang and T. Patel, “MicroRNA-Dependent Regulation of DNA Methyltransferase-1 and Tumor Suppressor Gene Expression by Interleukin-6 in Human Malignant Cholangiocytes,” Hepatology, Vol. 51, 2010, pp. 881-890.
F. Meng, R. Henson, M. Lang, H. Wehbe, S. Maheshwari, J. T. Mendell, J. Jiang, T. D. Schmittgen and T. Patel, “Involvement of Human Micro-RNA in Growth and Response to Chemotherapy in Human Cholangiocarcinoma Cell Lines,” Gastroenterology, Vol. 130, No. 7, 2006, pp. 2113-2129. doi:10.1053/j.gastro.2006.02.057
J. L. Mott, S. Kobayashi, S. F. Bronk and G. J. Gores, “Mir-29 Regulates Mcl-1 Protein Expression and Apoptosis,” Oncogene, Vol. 26, No. 42, 2007, pp. 6133-6140. doi:10.1038/sj.onc.1210436
F. Meng, H. Wehbe-Janek, R. Henson, H. Smith and T. Patel, “Epigenetic Regulation of MicroRNA-370 by Interleukin-6 in Malignant Human Cholangiocytes,” Oncogene, Vol. 27, 2007, pp. 378-386. doi:10.1038/sj.onc.1210648
H. Yang, T. W. Li, K. S. Ko, M. Xia and S. C. Lu, “Switch from Mnt-Max to Myc-Max Induces p53 and Cyclin D1 Expression and Apoptosis during Cholestasis in Mouse and Human Hepatocytes,” Hepatology, Vol. 49, No. 3, 2009, pp. 860-870. doi:10.1002/hep.22720
T. Masyuk, A. Masyuk and N. LaRusso, “MicroRNAs in Cholangiociliopathies,” Cell Cycle, Vol. 8, 2009, pp. 1324-1328. doi:10.4161/cc.8.9.8253
R. T. Moon, A. D. Kohn, G. V. De Ferrari and A. Kaykas, “WNT and Beta-Catenin Signalling: Diseases and Therapies,” Nature Reviews Genetics, Vol. 5, No. 9, 2004, pp. 691-701. doi:10.1038/nrg1427
K. S. Zaret, “Genetic Programming of Liver and Pancreas Progenitors: Lessons for Stem-Cell Differentiation,” Nature Reviews Genetics, Vol. 9, No. 5, 2008, pp. 329-340. doi:10.1038/nrg2318
N. Barker and H. Clevers, “Mining the Wnt Pathway for Cancer Therapeutics,” Nature Reviews Drug Discovery, Vol. 5, No. 12, 2006, pp. 997-1014. doi:10.1038/nrd2154
Y. Nakanuma, M. Sasaki, Y. Sato, X. Ren, H. Ikeda and K. Harada, “Multistep Carcinogenesis of Perihilar Cholangiocarcinoma Arising in the Intrahepatic Large Bile Ducts,” World journal of hepatology, Vol. 1, No. 1, 2009, pp. 35-42. doi:10.4254/wjh.v1.i1.35
S. Boyault, D. S. Rickman, A. de Reyniès, C. Balabaud, S. Rebouissou, E. Jeannot, A. Hérault, J. Saric, J. Belghiti, D. Franco, et al., “Transcriptome Classification of HCC is Related to Gene Alterations and to New Therapeutic Targets,” Hepatology, Vol. 45, No. 1, 2007, pp. 42-52. doi:10.1002/hep.21467
K. Itatsu, Y. Zen, J. Yamaguchi, S. Ohira, A. Ishikawa, H. Ikeda, Y. Sato, K. Harada, M. Sasaki, et al., “Expression of Matrix Metalloproteinase 7 is an Unfavorable Postoperative Prognostic Factor in Cholangiocarcinoma of the Perihilar, Hilar, and Extrahepatic Bile Ducts,” Human Pathology, Vol. 39, No. 5, 2008, pp. 710-719. doi:10.1016/j.humpath.2007.09.016
K. Sugimachi, K. Taguchi, S. Aishima, S. Tanaka, M. Shimada, K. Kajiyama, K. Sugimachi and M. Tsuneyoshi, “Altered Expression of Beta-Catenin without Genetic Mutation in Intrahepatic Cholangiocarcinoma,” Modern Pathology, Vol. 14, No. 9, 2001, pp. 900-905. doi:10.1038/modpathol.3880409
S. T. Hashimi, J. A. Fulcher, M. H. Chang, L. Gov, S. Wang and B. Lee, “MicroRNA Profiling Identifies miR-34a and miR-21 and Their Target Genes JAG1 and WNT1 in the Coordinate Regulation of Dendritic Cell Differentiation,” Blood, Vol. 114, 2009, pp. 404-414. doi:10.1182/blood-2008-09-179150
Y. Chen, W. Liu, T. Chao, Y. Zhang, X. Yan, Y. Gong, B. Qiang, J. Yuan, M. Sun and X. Peng, “MicroRNA-21 Down-Regulates the Expression of Tumor Suppressor PDCD4 in Human Glioblastoma Cell T98G,” Cancer Letters, Vol. 272, No. 2, 2008, pp. 197-205. doi:10.1016/j.canlet.2008.06.034
S. T. Hashimi, J. A. Fulcher, M. H. Chang, L. Gov, S. Wang and B. Lee, “MicroRNA Profiling Identifies miR-34a and miR-21 and Their Target Genes JAG1 and WNT1 in the Coordinate Regulation of Dendritic Cell Differentiation,” Blood, Vol. 114, 2009, No. 404-414. doi:10.1182/blood-2008-09-179150
Y. Chen, W. Liu, T. Chao, Y. Zhang, X. Yan, Y. Gong, B. Qiang, J. Yuan, M. Sun, X. Peng, “MicroRNA-21 Down-Regulates the Expression of Tumor Suppressor PDCD4 in Human Glioblastoma Cell T98G,” Cancer Letters, Vol. 272, No. 2, 2008, No. 197-205. doi:10.1016/j.canlet.2008.06.034
Q. Yao, H. Xu, Q. Q. Zhang, H. Zhou, L. H. Qu, “Mi-croRNA-21 Promotes Cell Proliferation and Down-Regulates the Expression of Programmed Cell Death 4 (PDCD4) in HeLa Cervical Carcinoma Cells,” Bio-chemical and Biophysical Research Communications, Vol. 388, No. 3, 2009, pp. 539-542. doi:10.1016/j.bbrc.2009.08.044
Z. Zhang, Z. Li, C. Gao, P. Chen, J. Chen, W. Liu, S. Xiao and H. Lu, “miR-21 Plays a Pivotal Role in Gastric Cancer Pathogenesis and Progression,” Laboratory Investigation, Vol. 88, No. 12, 2008, pp. 1358-1366. doi:10.1038/labinvest.2008.94
Y. J. Kim, S. J. Hwang, Y. C. Bae and J. S. Jung, “MiR-21 Regulates Adipogenic Differentiation through the Modulation of TGF-beta Signaling in Mesenchymal Stem Cells Derived from Human Adipose Tissue,” Stem Cells, Vol. 27, No. 12, 2009, pp. 3093-3102.
T. Papagiannakopoulos, A. Shapiro and K. S. Kosik, “MicroRNA-21 Targets a Network of Key Tumor-Suppressive Pathways in Glioblastoma Cells,” Cancer Research, Vol. 68, No. 19, 2008, pp. 8164-8172. doi:10.1158/0008-5472.CAN-08-1305
J. Zheng, H. Xue, T. Wang, Y. Jiang, B. Liu, J. Li, Y. Liu, W. Wang, B. Zhang and M. Sun, “MiR-21 Downregulates the Tumor Suppressor P12 CDK2AP1 and Stimulates Cell Proliferation and Invasion,” Journal of Cellular Biochemistry, Vol. 112, No. 3, 2011, pp. 872-880. doi:10.1002/jcb.22995
M. Korpal, E. S. Lee, G. Hu and Y. Kang, “The MiR-200 Family Inhibits Epithelial-Mesenchymal Transition and Cancer Cell Migration by Direct Targeting of E-Cadherin Transcriptional Repressors ZEB1 and ZEB2,” The Journal of Biological Chemistry, Vol. 283, No. 22, 2008, pp. 14910-14914. doi:10.1074/jbc.C800074200
U. Burk, J. Schubert, U. Wellner, O. Schmalhofer, E. Vincan, S. Spaderna and T. Brabletz, “A Reciprocal Repression between ZEB1 and Members of the miR-200 Family Promotes EMT and Invasion in Cancer Cells,” EMBO Reports, Vol. 9, No. 6, 2008, 582-589. doi:10.1038/embor.2008.74
P. A. Gregory, A. G. Bert, E. L. Paterson, S. C. Barry, A. Tsykin, G. Farshid, M. A. Vadas, Y. Khew-Goodall and G. J. Goodall, “The miR-200 Family and miR-205 Regulate Epithelial to Mesenchymal Transition by Targeting ZEB1 and SIP1,” Nature Cell Biology, Vol. 10, No. 5, 2008, 593-601. doi:10.1038/ncb1722
D. Kong, Y. Li, Z. Wang, S. Banerjee, A. Ahmad, H. R. Kim and F. H. Sarkar, “MiR-200 Regulates PDGF-D- Mediated Epithelial-Mesenchymal Transition, Adhesion, and Invasion of Prostate Cancer Cells,” Stem Cells, Vol. 27, No. 8, 2009, pp. 1712-1721. doi:10.1002/stem.101
S. M. Park, A. B. Gaur, E. Lengyel and M. E. Peter, “The miR-200 Family Determines the Epithelial Phenotype of Cancer Cells by Targeting the E-cadherin Repressors ZEB1 and ZEB2,” Genes & Development, Vol. 22, No. 7, 2008, pp. 894-907. doi:10.1101/gad.1640608
V. P. Tryndyak, F. A. Beland and I. P. Pogribny, “E-Cadherin Transcriptional Down-Regulation by Epigenetic and MicroRNA-200 Family Alterations is Related to Mesenchymal and Drug-Resistant Phenotypes in Human Breast Cancer Cells,” International Journal of Can-cer, Vol. 126, 2010, pp. 2575-2583.
O. Saydam, Y. Shen, T. Würdinger, O. Senol, E. Boke, M. F. James, B. A. Tannous, A. O. Stemmer-Rachamimov, M. Yi, R. M. Stephens, et al., “Downregulated Microrna-200a in Meningiomas Promotes Tumor Growth by Reducing E-Cadherin and Activating the Wnt/beta-Catenin Signaling Pathway,” Molecular and Cellular Biology, Vol. 29, No. 21, 2009, pp. 5923-5940. doi:10.1128/MCB.00332-09
M. Korpal, E. S. Lee, G. Hu and Y. Kang, “The miR-200 Family Inhibits Epithelial-Mesenchymal Transition and Cancer Cell Migration by Direct Targeting Of E-Cadherin Transcriptional Repressors ZEB1 and ZEB2,” The Journal of Biological Chemistry, Vol. 283, No. 22, 2008, pp. 14910-14914. doi:10.1074/jbc.C800074200
U. Burk, J. Schubert, U. Wellner, O. Schmalhofer, E. Vincan, S. Spaderna and T. Brabletz, “A Reciprocal Repression between ZEB1 and Members of the miR-200 Family Promotes EMT and Invasion in Cancer Cells,” EMBO Reports, Vol. 9, 2008, pp. 582-589. doi:10.1038/embor.2008.74
P. A. Gregory, A. G. Bert, E. L. Paterson, S. C. Barry, A. Tsykin, G. Farshid, M. A. Vadas, Y. Khew-Goodall and G. J. Goodall, “The miR-200 Family and miR-205 Regulate Epithelial to Mesenchymal Transition by Targeting ZEB1 and SIP1,” Nature Cell Biology, Vol. 10, No. 5, 2008, pp. 593-601. doi:10.1038/ncb1722
D. Kong, Y. Li, Z. Wang, S. Banerjee, A. Ahmad, H. R. Kim and F. H. Sarkar, “MiR-200 Regulates PDGF-D- Mediated Epithelial-Mesenchymal Transition, Adhesion, and Invasion of Prostate Cancer Cells,” Stem Cells, Vol. 27, No. 8, 2009, pp. 1712-1721. doi:10.1002/stem.101
S. M. Park, A. B. Gaur, E. Lengyel and M. E. Peter, “The miR-200 Family Determines the Epithelial Phenotype of Cancer Cells by Targeting the E-Cadherin Repressors ZEB1 and ZEB2,” Genes & Development, Vol. 22, No. 7, 2008, pp. 894-907. doi:10.1101/gad.1640608
V. P. Tryndyak, F. A. Beland and I. P. Pogribny, “Ecadherin Transcriptional Down-Regulation by Epigenetic and microRNA-200 Family Alterations is Related to Mesenchymal and Drug-Resistant Phenotypes in Human Breast Cancer Cells,” International Journal of Cancer, Vol. 126, No. 11, 2010, pp. 2575-2583.
O. Saydam, Y. Shen, T. Würdinger, O. Senol, E. Boke, M. F. James, B. A. Tannous, A. O. Stemmer-Rachamimov, M. Yi, R. M. Stephens, et al., “Downregulated microRNA-200a in Meningiomas Promotes Tumor Growth by Reducing E-Cadherin and Activating the Wnt/beta- Catenin Signaling Pathway,” Molecular and Cellular Biology, Vol. 29, No. 21, 2009, pp. 5923-5940. doi:10.1128/MCB.00332-09
C. J. Sherr, “Cancer cell cycles,” Science, Vol. 274, No. 5293, 1996, pp. 1672-1677. doi:10.1126/science.274.5293.1672
A. B. Pardee, “G1 Events and Regulation of Cell Proliferation,” Science, Vol. 246, No. 4930, 1989, pp. 603-608. doi:10.1126/science.2683075
H. Matsushime, M. E. Ewen, D. K. Strom, J. Y. Kato, S. K. Hanks, M. F. Roussel and C. J. Sherr, “Identification and Properties of an Atypical Catalytic Subunit (p34PSK-J3/cdk4) for Mammalian D Type G1 Cyclins,” Cell, Vol. 71, 1992, pp. 323-334. doi:10.1016/0092-8674(92)90360-O
M. Serrano, G. J. Hannon and D. Beach, “A New Regulatory Motif in Cell-Cycle Control Causing Specific Inhibition of Cyclin D/CDK4,” Nature, Vol. 366, No. 6456, 1993, pp. 704-707. doi:10.1038/366704a0
S. Waga, G. J. Hannon, D. Beach and B. Stillman, “The p21 Inhibitor of Cyclin-Dependent Kinases Controls DNA Replication by Interaction with PCNA,” Nature, Vol. 369, 1994, pp. 574-578. doi:10.1038/369574a0
W. S. el-Deiry, J. W. Harper, P. M. O'Connor, V. E. Velculescu, C. E. Canman, J. Jackman, J. A. Pietenpol, M. Burrell, D. E. Hill and Y. Wang, “WAF1/CIP1 is Induced in p53-Mediated G1 Arrest and Apoptosis,” Cancer Research, Vol. 54, No. 5, 1994, No. 1169-1174.
A. Ishikawa, M. Sasaki, Y. Sato, S. Ohira, M. F. Chen, S. F. Huang, K. Oda, Y. Nimura and Y. Nakanuma, “Frequent p16ink4a Inactivation is an Early and Frequent Event of Intraductal Papillary Neoplasm of the Liver Arising in Hepatolithiasis,” Human Pathology, Vol. 35, No. 12, 2004, pp. 1505-1514. doi:10.1016/j.humpath.2004.08.014
Y. Nakanishi, Y. Zen, S. Kondo, T. Itoh, K. Itatsu and Y. Nakanuma, “Expression of Cell Cycle-Related Molecules in Biliary Premalignant Lesions: Biliary Intraepithelial Neoplasia and Biliary Intraductal Papillary Neoplasm,” Human Pathology, Vol. 39, No. 8, 2008, pp. 1153-1161.doi:10.1016/j.humpath.2007.11.018
K. Itatsu, M. Sasaki, K. Harada, J. Yamaguchi, H. Ikeda, Y. Sato, T. Ohta, H. Sato, M. Nagino, Y. Nimura, et al., “Phosphorylation of Extracellular Signal-Regulated Kinase 1/2, p38 Mitogen-Activated Protein Kinase and Nuclear Translocation of Nuclear FactorkappaB are Involved in Upregulation of Matrix Metalloproteinase-9 by Tumour Necrosis Factor-alpha,” Liver International, Vol. 29, No. 2, 2009, pp. 291-298. doi:10.1111/j.1478-3231.2008.01858.x
C. Welch, Y. Chen and R. L. Stallings, “MicroRNA-34a Functions as a Potential Tumor Suppressor by Inducing Apoptosis in Neuroblastoma Cells,” Oncogene, Vol. 26, 2007, pp. 5017-5022. doi:10.1038/sj.onc.1210293
H. Tazawa, N. Tsuchiya, M. Izumiya and H. Nakagama, “Tumor-Suppressive miR-34a Induces Senescence-Like Growth Arrest through Modulation of the E2F Pathway in Human Colon Cancer Cells,” Proceedings of the National Academy of Sciences USA, Vol. 104, No. 39, 2007, pp. 15472-15477. doi:10.1073/pnas.0707351104
O. Merkel, D. Asslaber, J. D. Pi?ón, A. Eglea and R. Greil, “Interdependent Regulation of p53 and miR-34a in Chronic Lymphocytic Leukemia,” Cell Cycle, Vol. 9, 2010, pp. 2764-2768. doi:10.4161/cc.9.14.12267
T. C. Chang, E. A. Wentzel, O. A. Kent, K. Ramachandran, M. Mullendore, K. H. Lee, G. Feldmann, M. Yamakuchi, M. Ferlito, C. J. Lowenstein, et al., “Transactivation of miR-34a by p53 Broadly Influences Gene Expression and Promotes Apoptosis,” Molecular Cell, Vol. 26, No. 5, 2007, pp. 745-752. doi:10.1016/j.molcel.2007.05.010
N. Raver-Shapira, E. Marciano, E. Meiri, Y. Spector, N. Rosenfeld, N. Moskovits, Z. Bentwich and M. Oren, “Transcriptional Activation of miR-34a Contributes to p53-Mediated Apoptosis,” Molecular Cell, Vol. 26, 2007, pp. 731-743. doi:10.1016/j.molcel.2007.05.017
V. Tarasov, P. Jung, B. Verdoodt, D. Lodygin, A. Epan-chintsev, A. Menssen, G. Meister and H. Hermeking, “Differential Regulation of microRNAs by p53 Revealed by Massively Parallel Sequencing: miR-34a is a p53 Target that Induces Apoptosis and G1-arrest,” Cell Cycle, Vol. 6, 2007, pp. 1586-1593. doi:10.4161/cc.6.13.4436
M. Fabbri, A. Bottoni, M. Shimizu, R. Spizzo, M. S. Nicoloso, S. Rossi, E. Barbarotto, A. Cimmino, B. Adair, S. E. Wojcik, et al., “Association of a microRNA/TP53 Feedback Circuitry with Pathogenesis and Outcome of B-cell Chronic Lymphocytic Leukemia,” The Journal of the American Medical Association, Vol. 305, No. 1, 2011, pp. 59-67. doi:10.1001/jama.2010.1919
Y. Wang, C. G. Lee, “MicroRNA and Cancer—Focus on Apoptosis,” Journal of Cellular and Molecular Medicine, Vol. 13, No. 1, 2009, pp. 12-23. doi:10.1111/j.1582-4934.2008.00510.x
S. W. Lowe and A. W. Lin, “Apoptosis in cancer,” Carcinogenesis, Vol. 21, No. 3, 2000, pp. 485-495. doi:10.1093/carcin/21.3.485
M. Sasaki, J. Yamaguchi, K. Itatsu, H. Ikeda and Y. Nakanuma, “Over-Expression of Polycomb Group Protein EZH2 Relates to Decreased Expression of p16 INK4a in Cholangiocarcinogenesis in Hepatolithiasis,” The Journal of Pathology, Vol. 215, No. 2, 2008, pp. 175-183. doi:10.1002/path.2345
Y. Zen, K. Harada, M. Sasaki, K. Tsuneyama, K. Kata-yanagi, Y. Yamamoto and Y. Nakanuma, “Lipopolysaccharide Induces Overexpression of MUC2 and MUC5AC in Cultured Biliary Epithelial Cells: Possible Key Phenomenon of Hepatolithiasis,” American Journal of Pathology, Vol. 161, No. 4, 2002, pp. 1475-1484. doi:10.1016/S0002-9440(10)64423-9
S. Dangi-Garimella, M. J. Strouch, P. J. Grippo, D. J. Bentrem and H. G. Munshi, “Collagen Regulation of Let-7 in Pancreatic Cancer Involves TGF-β1-Mediated Membrane Type 1-Matrix Metalloproteinase Expression,” Oncogene, Vol. 30, No. 8, 2011, pp. 1002-1008. doi:10.1038/onc.2010.485
Y. Kodama, M. Hijikata, R. Kageyama, K. Shimotohno, T. Chiba, “The Role of Notch Signaling in the Development of Intrahepatic Bile Ducts,” Gastroenterology, Vol. 127, No. 6, 2004, pp. 1775-1786. doi:10.1053/j.gastro.2004.09.004
V. Bolos, J. Grego-Bessa and J. L. de la Pompa, “Notch Signaling in Development and Cancer,” Endocrine Reviews, Vol. 28, No. 3, 2007, pp. 339-363. doi:10.1210/er.2006-0046
N. Ishimura, S. F. Bronk and G. J. Gores, “Inducible Nitric Oxide Synthase Up-Regulates Notch-1 in Mouse Cholangiocytes: Implications for Carcinogenesis,” Gastroenterology, Vol. 128, No. 5, 2005, pp. 1354-1368. doi:10.1053/j.gastro.2005.01.055
H. Francis, G. Alpini and S. DeMorrow, “Recent Advances in the Regulation of Cholangiocarcinoma Growth,” American Journal of Physiology-Gastrointestinal and Liver Physiology, Vol. 299, No. 1, 2010, pp. G1-G9. doi:10.1152/ajpgi.00114.2010
F. Guessous, Y. Zhang, A. Kofman, A. Catania, Y. Li, D. Schiff, B. Purow and R. Abounader, “MicroRNA-34a is Tumor Suppressive in Brain Tumors and Glioma Stem Cells,” Cell Cycle, Vol. 9, No. 6, 2010, pp. 1031-1036. doi:10.4161/cc.9.6.10987
P. W. Ingham and A. P. McMahon, “Hedgehog Signaling in Animal Development: Paradigms and Principles,” Genes & Development, Vol. 15, No. 23, 2001, pp. 3059-3087. doi:10.1101/gad.938601
K. Koebernick and T. Pieler, “Gli-Type Zinc Finger Proteins as Bipotential Transducers of Hedgehog Signaling,” Differentiation, Vol. 70, No. 2-3, 2002, pp. 69-76. doi:10.1046/j.1432-0436.2002.700201.x
N. Oishi and X. W. Wang, “Novel Therapeutic Strategies for Targeting Liver Cancer Stem Cells,” International Journal of Biological Sciences, Vol. 7, No. 5, 2011, pp. 517-535. doi:10.7150/ijbs.7.517
C. Osipo and L. Miele, “Hedgehog Signaling in Hepato-cellular Carcinoma: Novel Therapeutic Strategy Targeting Hedgehog Signaling in HCC,” Cancer Biology and Therapy, Vol. 5, No. 2, 2006, pp. 238-239. doi:10.4161/cbt.5.2.2566
L. Yang, G. Xie, Q. Fan and J. Xie, “Activation of the Hedgehog-Signaling Pathway in Human Cancer and the Clinical Implications” Oncogene, Vol. 29, No. 4, 2010, pp. 469-481. doi:10.1038/onc.2009.392
T. Uziel, F. V. Karginov, S. Xie, J. S. Parker, Y. D. Wang, A. Gajjar, L. He, D. Ellison, R. J. Gilbertson, G. Hannon and M. F. Roussel, “The miR-17~92 Cluster Collaborates with the Sonic Hedgehog Pathway in Medulloblastoma,” Proceedings of the National Academy of Sciences USA, Vol. 106, No. 8, 2009, pp. 2812-2817. doi:10.1073/pnas.0809579106
A. Omenetti, A. Porrello, Y. Jung, L. Yang, Y. Popov, S.S. Choi, et al., “Hedgehog Signaling Regulates Epithelial-Mesenchymal Transition during Biliary Fibrosis in Rodents and Humans,” The Journal of Clinical Investigation, Vol. 118, No. 10, 2008, pp. 3331-3342.
A. Omenetti, Y. Popov, Y. Jung, S. S. Choi, R. P. Witek, L. Yang, et al., “The Hedgehog Pathway Regulates Remodeling Responses to Biliary Obstruction in Rats,” International Journal of Gastroenterology & Hepatology, Vol. 57, No. 9, 2008, pp. 1275-1282. doi:10.1136/gut.2008.148619
A. Omenetti, L. Yang, Y. X. Li, S. J. McCall, Y. Jung, J. K. Sicklick, et al., “Hedgehog-Mediated Mesenchymal-Epithelial Interactions Modulate Hepatic Response to Bile Duct Ligation,” Laboratory Investigation, Vol. 87, No. 5, 2007, pp. 499-514.
Y. Jung, S. J. McCall, Y. X. Li and A. M. Diehl, “Bile Ductules and Stromal Cells Express Hedgehog Ligands and/or Hedgehog Target Genes in Primary Biliary Cirrhosis,” Hepatology, Vol. 45, No. 5, 2007, pp. 1091-1096. doi:10.1002/hep.21660
A. Omenetti and A. M. Diehl, “Hedgehog Signaling in Cholangiocytes,” Current Opinion in Gastroenterology, Vol. 27, 2011, pp. 268-275. doi:10.1097/MOG.0b013e32834550b4
A. S. Flynt, N. Li, E. J. Thatcher, L. Solnica-Krezel and J. G. Patton, “Zebrafish miR-214 Modulates Hedgehog Signaling to Specify Muscle Cell Fate,” Nature Genetics, Vol. 39, No. 2, 2007, pp. 259-263. doi:10.1038/ng1953
H. Yang, W. Kong, L. He, et al., “MicroRNA Expression Profiling in Human Ovarian Cancer: miR-214 Induces Cell Survival and Cisplatin Resistance by Targeting PTEN,” Cancer Research, Vol. 68, No. 2, 2008, pp. 425- 433. doi:10.1158/0008-5472.CAN-07-6426
R. Amin and L. Mishra, “Liver Stem Cells and tgf-Beta in Hepatic Carcinogenesis,” Gastrointest Cancer Research, Vol. 2, 2008, pp. S27-S30.
Y. Tang, K. Kitisin, W. Jogunoori, C. Li, C. X. Deng and S. C. Mueller, et al., “Progenitor/Stem Cells Give Rise to Liver Cancer due to Aberrant TGF-beta and IL-6 Signaling,” Proceedings of the National Academy of Sciences USA, Vol. 105, No. 7, 2008, pp. 2445-2450. doi:10.1073/pnas.0705395105
L. Mishra, R. Derynck and B. Mishra, “Transforming Growth Factor-beta Signaling in Stem Cells and Cancer,” Science, Vol. 310, No. 5745, 2005, pp. 68-71. doi:10.1126/science.1118389
K. Breuhahn, T. Longerich and P. Schirmacher, “Dysregulation of Growth Factor Signaling in Human Hepatocellular Carcinoma,” Oncogene, Vol. 25, 2006, pp. 3787-3800. doi:10.1038/sj.onc.1209556
H. G. Kim, Y. H. Chung, B. C. Song, J. Kim, S. H. Yang, Y. S. Lee and D. J. Suh, “Expression of Transforming Growth Factor beta-1 in Chronic Hepatitis and Hepatocellular Carcinoma Associated with Hepatitis C Virus Infection,” The Korean Journal of Internal Medicine, Vol. 15, No. 3, 2000, pp. 165-170.
J. F. Tsai, J. E. Jeng, L. Y. Chuang, et al., “Elevated Urinary Transforming Growth Factor-beta1 Level as a Tumour Marker and Predictor of Poor Survival in Cirrhotic Hepatocellular Carcinoma,” British Journal of Cancer, Vol. 76, No. 2, 1997, pp. 244-250. doi:10.1038/bjc.1997.369
Y. Lu, L. Q. Wu, C. S. Li, et al., “Expression of Transforming Growth Factors in Hepatocellular Carcinoma and Its Relations with Clinicopathological Parameters and Prognosis,” Hepatobiliary & Pancreatic Diseases International, Vol. 7, 2008, pp. 174-178.
M. Ikeguchi, A. Iwamoto, K. Taniguchi, et al., “The Gene Expression Level of Transforming Growth Factor-beta (TGF-beta) as a Biological Prognostic Marker of Hepatocellular Carcinoma,” Journal of Experimental & Clinical Cancer Research, Vol. 24, No. 3, 2005, pp. 415-421
Y. Shirai, S. Kawata, S. Tamura, N. Ito, H. Tsushima, K. Takaishi, S. Kiso and Y. Matsuzawa, “Plasma Transforming Growth Factor-beta 1 in Patients with Hepatocellular Carcinoma. Comparison with Chronic Liver Diseases,” Cancer, Vol. 73, No. 9, 1994, pp. 2275-2279. doi:10.1002/1097-0142(19940501)73:9 3.0.CO;2-T
J. P. Lu, J. Q. Mao, M. S. Li, S. L. Lu, X. Q. Hu, S. N. Zhu and S. Nomura, “In situ Detection of TGF Betas, TGF Beta Receptor II mRNA and Telomerase Activity in Rat Cholangiocarcinogenesis,” World Journal of Gastroenterology, Vol. 9, No. 3, 2003, pp. 590-594.
C. Benckert, S. Jonas, T. Cramer, Z. Von Marschall, G. Schafer, M. Peters, K. Wagner, C. Radke, B. Wiedenmann, P. Neuhaus, et al., “Transforming Growth Factor Beta 1 Stimulates Vascular Endothelial Growth Factor Gene Transcription in Human Cholangiocellular Carcinoma Cells,” Cancer Research, Vol. 63, No. 5, 2003, pp. 1083-1092
Y. Zen, K. Harada, M. Sasaki, T. Chen, M. Chen, T. Yeh, Y. Jan, S. Huang, Y. Nimura and Y. Nakamura, “Intrahepatic Cholangiocarcinoma Escapes from Growth Inhibitory Effect of Transforming Growth Factor-beta1 by Overexpression of Cyclin D1,” Laboratory Investigation, Vol. 85, No. 4, 2005, pp. 572-581. doi:10.1038/labinvest.3700236
M. E. Burlone and A. Budkowska, “Hepatitis C Virus Cell Entry Role of Lipoproteins and Cellular Receptors,” Journal of General Virology, Vol. 90, No. 5, 2009, pp. 1055-1070. doi:10.1099/vir.0.008300-0
M. Nassal and B. Hepatitis, “Viruses: Reverse Transcription a Different Way,” Virus Research, Vol. 134, No. 1-2, 2008, pp. 235-249. doi:10.1016/j.virusres.2007.12.024
Z. H. Liu and J. L. Hou, “Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) Dual Infection,” International Journal of Medical Sciences, Vol. 3, No. 2, 2006, pp. 57- 62. doi:10.7150/ijms.3.57
D. P. Bartel, “MicroRNAs: Genomics, Biogenesis, Mechanism, and Function,” Cell, Vol. 116, 2004, pp. 281- 297. doi:10.1016/S0092-8674(04)00045-5
N. Bushati and S. M. Cohen, “MicroRNA functions,” Annual Review of Cell and Developmental Biology, Vol. 23, 2007, pp. 175-205. doi:10.1146/annurev.cellbio.23.090506.123406
J. M. Thomson, M. Newman, J. S. Parker, E. M. Morin-Kensicki, T. Wright and S. M. Hammond, “Extensive Post-Transcriptional Regulation of microRNAs and Its Implications for Cancer,” Genes & Development, Vol. 20, No. 16, 2006, pp. 2202-2207. doi:10.1101/gad.1444406
M. L. Yeung, Y. Bennasser, T. G. Myers, G. J. Jiang, M. Benkirane and K. T. Jeang, “Changes in microRNA Expression Profiles in HIV 1 Transfected,” Retrovirology, Vol. 2, No. 2, 2005, p. 81. doi:10.1186/1742-4690-2-S1-S81
A. Gupta, J. J. Gartner, P. Sethupathy, A. G. Hatzigeorgiou, N. W. Fraser, “Anti-Apoptotic Function of a microRNA Encoded by the HSV1 Latency-Associated Transcript,” Nature, Vol. 442, No. 7098, 2006, pp. 82-85.
Z. Ghosh, B. Mallick and J. Chakrabarti, “Cellular versus Viral microRNAs in Host-Virus Interaction,” Nucleic Acids Research, Vol. 37, No. 4, 2009, No. 1035-1048. doi:10.1093/nar/gkn1004
O. Voinnet, “Induction and Suppression of RNA Silencing: Insights from Viral Infections,” Nature Reviews Genetics, Vol. 6, No. 3, 2005, pp. 206-220. doi:10.1038/nrg1555
R. L. Skalsky and B. R. Cullen, “Viruses, microRNAs, and Host Interactions,” Annual Review of Microbiology, Vol. 64, 2010, pp. 123-141. doi:10.1146/annurev.micro.112408.134243
Y. Bennasser, M. L. Yeung and K. T. Jeang, “HIV-1 TAR RNA Subverts RNA Interference in Transfected Cells through Sequestration of TAR RNA-binding Protein TRBP,” The Journal of Biological Chemistry, Vol. 281, No. 38, 2006, pp. 27674-27678. doi:10.1074/jbc.C600072200
S. Pfeffera and T. F. Baumert, “Impact of microRNAs for Pathogenesis and Treatment of Hepatitis C Virus Infection,” Gastroentérologie Clinique et Biologique, Vol. 34, No. 8-9, 2010, pp. 431-435. doi:10.1016/j.gcb.2010.04.010
P. Sarnow, C. L. Jopling, K. L. Norman, S. Schütz and K. A.Wehner, “MicroRNAs Expression, Avoidance and Subversion by Vertebrate Viruses,” Nature Reviews, Vol. 4, No. 9, 2006, pp. 651-659. doi:10.1038/nrmicro1473
E. Gottwein and B. R. Cullen, “Viral and Cellular microRNAs as Determinants of Viral Pathogenesis and Immunity,” Cell Host & Microbe, Vol. 3, No. 6, 2008, pp. 375-387. doi:10.1016/j.chom.2008.05.002
W. B. Jin and F. L. Wu, “HBV-Encoded microRNA Candidate and Its Target,” Computational Biology and Chemistry, Vol. 31, No. 2, 2007, pp. 124-126. doi:10.1016/j.compbiolchem.2007.01.005
M. Honda, T. Yamashita, T. Ueda, H. Takatori, R. Nishino and S. Kaneko, “Different Signaling Pathways in the Livers of Patients with Chronic Hepatitis B or Chronic Hepatitis C,” Hepatology, Vol. 44, No. 5, 2006, pp. 1122-1138. doi:10.1002/hep.21383
C. Braconi, N. Valeri, P. Gasparini, N. Y. Huang, C. Taccioli, G. Nuovo, T. Suzuki, C. M. Croce and T. Patel, “Hepatitis C Virus Proteins Modulate MicroRNA Expression and Chemosensitivity in Malignant Hepatocytes,” Clinical Cancer Research, Vol. 16, No. 3, 2010, pp. 957-966. doi:10.1158/1078-0432.CCR-09-2123
X. X. Peng, Y. Li, K. A. Walters, E. R. Rosenzweig, S. L. Lederer, L. D. Aicher, S. Proll and M. G. Katze, “Computational Identification of Hepatitis C Virus Associated microRNA-mRNA Regulatory Modules in Human Livers,” BMC Genomics, Vol. 10, 2009, p. 373. doi:10.1186/1471-2164-10-373
X. Y. Liu, T. Y. Wang, T. Wakita and W. Yang, “Systematic Identification of microRNA and Messenger RNA Profiles in Hepatitis C Virus-Infected Human Hepatoma Cells,” Virology, Vol. 398, No. 1, 2010, No. 57-67. doi:10.1016/j.virol.2009.11.036
N. M. Steuerwald, J. C. Parsons, K. Bennett, T. C. Bates and H. L. Bonkovsky, “Parallel microRNA and mRNA Expression Profiling of (genotype 1b) Human Hepatoma Cells Expressing Hepatitis C Virus,” Liver International, Vol. 30, No. 10, 2010, pp. 1490-1504. doi:10.1111/j.1478-3231.2010.02321.x
Y. Liu, J. J. Zhao, C. M. Wang, M. Y. Li, P. Hang, L. Wang, Y. Q. Chen, F. Zoulim, X. Ma and D. P. Xu, “Altered Expression Profiles of microRNAs in a Stable Hepatitis B Virus-Expressing Cell Line,” Chinese Medical Journal, Vol. 122, No. 1, 2009, pp. 10-14. doi:10.3901/JME.2009.11.010
H. T. Zhu, Q. Z. Dong, G. Wang, H. J. Zhou, N. Ren, H. L. Jia, Q. H. Ye and L. X. Qin, “Identification of Suitable Reference Genes for qRT-PCR Analysis of Circulating microRNAs in Hepatitis B Virus-Infected Patients,” Molecular Biotechnology, Vol. 50, No. 1, 2012, pp. 49-56. doi:10.1007/s12033-011-9414-6
S. Ura, M. Honda, T. Yamashita, T. Ueda, H. Takatori, R. Nishino, H. Sunakozaka, Y. Sakai, K. Horimoto and S. Kaneko, “Differential microRNA Expression between Hepatitis B and Hepatitis C Leading Disease Progression to Hepatocellular Carcinoma,” Hepatology, Vol. 49, No. 4, 2009, pp. 1098-1112. doi:10.1002/hep.22749
M. Lagos-Quintana, R. Rauhut, A. Yalcin, J. Meyer, W. Lendeckel and T. Tuschl, “Identification of Tissue-Specific microRNAs from Mouse,” Current Biology, Vol. 12, No. 9, 2002, pp. 735-739. doi:10.1016/S0960-9822(02)00809-6
C. L. Jopling, M. K. Yi, A. M. Lancaster, S. M. Lemon and P. Sarnow, “Modulation of Hepatitis C Virus RNA Abundance by a Liver-Specific micro-RNA,” Science, Vol. 309, No. 5740, 2005, pp. 1577-1581. doi:10.1126/science.1113329
C. L. Jopling, S. Schütz and P. Sarnow, “Position-Dependent Function for a Tandem microRNA miR-122- binding Site Located in the Hepatitis C Virus RNA Genome,” Cell Host & Microbe, Vol. 4, 2008, pp. 77-85. doi:10.1016/j.chom.2008.05.013
K. Shruti, K. Shrey and R. Vibha, “Micro RNAs: Tiny Sequences with Enormous Potential,” Biochemical and Biophysical Research Communications, Vol. 407, No. 4, 2011, pp. 445-449. doi:10.1016/j.bbrc.2011.03.058
E. S. Machlin, P. Sarnow and S. M. Sagan, “Masking the 5′ Terminal Nucleotides of the Hepatitis C Virus Genome by an Unconventional microRNA-target RNA Complex,” Proceedings of the National Academy of Sciences USA, Vol. 108, No. 8, 2011, pp. 3193-3198. doi:10.1073/pnas.1012464108
J. A. Wilson, C. Zhang, A. Huys and C. D. Richardson, “Human Ago2 Is Required for Efficient MicroRNA 122 Regulation of Hepatitis C Viru s RNA Accumulation and Translation,” Journal of Virology, Vol. 85, No. 5, 2011, pp. 2342-2350. doi:10.1128/JVI.02046-10
J. I. Henke, D. Goergen, J. Zheng, Y. Song, C. G. Schüttler, C. Fehr, C. Jünemann and M. Niepmann, “Micro-RNA-122 Stimulates Translation of Hepatitis C Virus RNA,” EMBO Journal, Vol. 27, No. 24, 2008, pp. 3300-3310. doi:10.1038/emboj.2008.244
M. Niepmann, “Activation of Hepatitis C Virus Translation by a Liver-Specific micro-RNA,” Cell Cycle, Vol. 8, No. 10, 2009, pp. 1473-1477. doi:10.4161/cc.8.10.8349
R. K. Jangra, M. K. Yi and S. M. Lemon, “Regulation of Hepatitis C Virus Translation and Infectious Virus Production,” Journal of Virology, Vol. 84, No. 13, 2010, pp. 6615-6625. doi:10.1128/JVI.00417-10
Y. Shan, J. Y. Zheng, R. W. Lambrecht and H. L. Bonkovsky, “Reciprocaleffects of micro-RNA-122 on Expression of Heme Oxygenase-1 and Hepatitis C Virus Genes in Human Hepatocytes,” Gastroenterology, Vol. 133, No. 4, 2007, pp. 1166-1174. doi:10.1053/j.gastro.2007.08.002
L. P. Qiu, H. X. Fan, W. S. Jin, B. Zhao, Y. Z. Wang, Y. Ju, L. Z. Chen, Y. Chen, Z. P. Duan and S. D. Meng, “MiR-122-Induced Down-Regulation of HO-1 Negatively Affects miR-122-Mediated Suppression of HBV,” Biochemical and Biophysical Research Communications, Vol. 398, No. 4, 2010, pp. 771-777. doi:10.1016/j.bbrc.2010.07.021
Y. Murakami, H. H. Aly, A. Tajima, I. Inoue and K. Shimotohno, “Regulation of the Hepatitis C Virus Genome Replication by miR-199a,” Journal of Hepatology, Vol. 50, No. 3, 2009, pp. 453-460. doi:10.1016/j.jhep.2008.06.010
G. L. Zhang, Y. X. Li, S. Q. Zheng, M. Liu, X. Li, H. Tang, “Suppression of Hepatitis B Virus Replication by microRNA-199a-3p and microRNA-210,” Antiviral Research, Vol. 88, No. 2, 2010, pp. 169-175. doi:10.1016/j.antiviral.2010.08.008
W. Hou, Q. Tian, J. Zheng and H. L. Bonkovsky, “Micro-RNA-196 Represses Bach1 Protein and Hepatitis C Virus Gene Expression in Human Hepatoma Cells Expressing Hepatitis C Viral Proteins,” Hepatology, Vol. 51, No. 5, 2010, pp. 1494-1504. doi:10.1002/hep.23401
N. M. Steuerwald, J. C. Parsons, K. Bennett, T. C. Bates and H. L. Bonkovsky, “Parallel microRNA and mRNA Expression Profiling of (genotype 1b) Human Hepatoma cells Expressing Hepatitis C Virus,” Liver International, Vol. 30, No. 10, 2010, pp. 1490-1504. doi:10.1111/j.1478-3231.2010.02321.x
K. Banaudha, M. Kaliszewski, T. Korolnek, L. Florea, M. L. Yeung, K. T. Jeang and A. Kumar, “MicroRNA Silencing of Tumor Suppressor DLC-1 Promotes Efficient Hepatitis C Virus Replication in Primary Human Hepatocytes,” Hepatology, Vol. 53, No. 1, 2011, pp. 53-61. doi:10.1002/hep.24016
X. Zhang, E. Zhang, Z. Ma, R. Pei, M. Jiang, J. F. Schlaak, M. Roggendorf and M. Lu, “Modulation of HBV Replication and Hepatocyte Differentiation by microRNA-1,” Hepatology, Vol. 53, No. 5, 2011, pp. 1476- 1485. doi:10.1002/hep.24195
N. Potenza, U. Papa, N. Mosca, F. Zerbini, V. Nobile and A. Russo, “Human microRNA hsa-miR-125a-5p Interferes with Expression of Hepatitis B Virus Surface Antigen,” Nucleic Acids Research, Vol. 39, No. 12, 2011, pp. 5157-5163. doi:10.1093/nar/gkr067
F. L. Wu, W. B. Jin, J. H. Li and A. G. Guo, “Targets for Human Encoded microRNAs in HBV Genes,” Virus Genes, Vol. 42, No. 2, 2011, pp. 157-161. doi:10.1007/s11262-010-0555-7
A. Tan, S. H. Yeh, C. J. Liu, C. Cheung and P. J. Chen, “Viral Hepatocarcinogenesis: From Infection to Cancer,” Liver International, Vol. 28, No. 2, 2008, pp. 175-188. doi:10.1111/j.1478-3231.2007.01652.x
Y. Ladeiro, G. Couchy, C. Balabaud, P. Bioulac-Sage, L. Pelletier, S. Rebouissou and J. Zucman-Rossi, “MicroRNA Profiling in Hepatocellular Tumors is Associated with Clinical Features and Oncogene/Tumor Suppressor Gene Mutations,” Hepatology, Vol. 47, No. 6, 2008, pp. 1955-1963. doi:10.1002/hep.22256
R. E. Lanford, E. S. Hildebrandt-Eriksen, A. Petri, R. Persson, M. Lindow, M. E. Munk, S. Kauppinen and H. Orum, “Therapeutic Silencing of microRNA-122 in Primates with Chronic Hepatitis C Virus Infection,” Science, Vol. 327, No. 5962, 2010, pp. 198-201. doi:10.1126/science.1178178
A. Tan, S. H. Yeh, C. J. Liu, C. Cheung and P. J. Chen, “Viral Hepatocarcinogenesis: From Infection to Cancer,” Liver Internatioanl, Vol. 28, No. 2, 2008, pp. 175-188. doi:10.1111/j.1478-3231.2007.01652.x
I. M. Pedersen, G. Cheng, S. Wieland, S. Volinia, C. M. Croce, F. V. Chisari and M. David, “Interferon Modulation of Cellular microRNAs as an Antiviral Mechanism,” Nature, Vol. 449, No. 7164, 2007, pp. 919-922. doi:10.1038/nature06205
C. Scagnolari, P. Zingariello, J. Vecchiet, C. Selvaggi, D. Racciatti, G. Taliani, E. Riva, E. Pizzigallo and G. Antonelli, “Differential Expression of Interferon-Induced microRNAs in Patients with Chronic Hepatitis C Virus Infection Treated with Pegylated Interferon Alpha,” Virology Journal, Vol. 7, No. 1, 2010, p. 311. doi:10.1186/1743-422X-7-311
Y. Murakami, M. Tanaka, H. Toyoda, K. Hayashi, M. Kuroda, A. Tajima and K. Shimotohno, “Hepatic microRNA Expression is Associated with the Response to Interferon Treatment of Chronic Hepatitis C,” BMC Medical Genomics, Vol. 3, No. 1, 2010, p. 48. doi:10.1186/1755-8794-3-48
V. S. Mahajan, A. Drake and J. Chen, “Virus-Specific Host miRNAs Antiviral Defenses or Promoters of Persistent Infection,” Trends in Immunology, Vol. 30, No. 1, 2009, pp. 1-7. doi:10.1016/j.it.2008.08.009
W. Li, L. Xie, X. He, J. Li, K. Tu, L. Wei, et al., “Diagnostic and Prognostic Implications of microRNAs in Human Hepatocellular Carcinoma,” International Journal of Cancer, Vol. 123, No. 7, 2008, pp. 1616-1622. doi:10.1002/ijc.23693
J. Jiang, Y. Gusev, I. Aderca, T. A. Mettler, D. M. Nagorney, D. J. Brackett, et al., “Association of MicroRNA Expression in Hepatocellular Carcinomas with Hepatitis Infection, Cirrhosis and Patient Survival,” Clinical Cancer Research, Vol. 14, No. 2, 2008, pp. 419-427. doi:10.1158/1078-0432.CCR-07-0523
H. Su, J. R. Yang, T. Xu, J. Huang, L. Xu, Y. Yuan and S. M. Zhuang, “MicroRNA-101, Downregulated in Hepatocellular Carcinoma, Promotes Apoptosis and Suppresses Tumorigenicity,” Cancer Research, Vol. 69, No. 3, 2009, pp. 1135-1142. doi:10.1158/0008-5472.CAN-08-2886
J. Ji, T. Yamashita, A. Budhu, M. Forgues, H. L. Jia, C. Li, et al., “Identification of microRNA-181 by Genome- Wide Screening as a Critical Player in EpCAM-Positive Hepatic Cancer Stem Cells,” Hepatology, Vol. 50, No. 2, 2009, pp. 472-480. doi:10.1002/hep.22989
H. Varnholt, U. Drebber, F. Schulze, I. Wedemeyer, P. Schirmacher, H. P. Dienes and M. Odenthal, “MicroRNA Gene Expression Profile of Hepatitis C Virus-Associated Hepatocellular Carcinoma,” Hepatology, Vol. 47, No. 4, 2008, pp. 1223-1232. doi:10.1002/hep.22158
A. Budhu, H. L. Jia, M. Forgues, C. G. Liu, D. Goldstein, A. Lam, K. A. Zanetti, Q. H. Ye, L. X. Qin, et al., “Identification of Metas-Tasis-Related microRNAs in Hepatocellular Carcinoma,” Hepatology, Vol. 47, No. 3, 2008, pp. 897-907. doi:10.1002/hep.22160
K. Z. Qu, K. Zhang, H. Li, N. H. Afdhala and M. Albitar, “Circulating microRNAs as Biomarkers for Hepatocellular Carcinoma,” Journal of Clinical Gastroenterology, Vol. 45, No. 4, 2011, pp. 355-360. doi:10.1097/MCG.0b013e3181f18ac2
Y. Yamamoto, N. Kosaka, M. Tanaka, et al., “MicroRNA-500 as a Potential Diagnostic Marker for Hepatocellular Carcinoma,” Biomarkers, Vol. 14, No. 7, 2009, pp. 529-538 doi:10.3109/13547500903150771
J. Li, Y. Wang, W. Yu, J. Chen and J. Luo, “Expression of Serum miR-221 in Human Hepatocellular Carcinoma and Its Prognostic Significance,” Biochemical and Biophysical Research Communications, Vol. 406, No. 1, 2011, pp. 70-73. doi:10.1016/j.bbrc.2011.01.111
B. S. Sun, Q. Z. Dong, Q. H. Ye, H. J. Sun, H. L. Jia, X. Q. Zhu, et al., “Lentiviral-Mediated miRNA against Osteopontin Suppresses Tumor Growth and Metastasis of Human Hepatocellular Carcinoma,” Hepatology, Vol. 48, No. 6, 2008, pp. 1834-1842. doi:10.1002/hep.22531