Meningiomas are common primary tumors of the central nervous system, affecting the intracranial and spinal dural surfaces. Multiple meningiomas account for approximately 1% to 10% of diagnosed cases and may occur synchronously or metachronously, being associated with alterations in the NF2 gene or arising sporadically. To date, little is known about the pathophysiology of these tumors. The capacity for pluripotency and self-renewal are well-known characteristics of embryonic stem cells, regulated by the transcription factors SOX2, OCT4, and NANOG, which govern the stem phenotype. One hypothesis of tumor development is that tumor stem cells exhibit a phenotype similar to embryonic stem cells; therefore, understanding the role of these transcription factors is crucial for elucidating mechanisms involved in tumor development. MicroRNAs also participate in regulating factors associated with pluripotency, presenting themselves as potential markers involved in this regulatory axis. Our objective was to evaluate the expression of the microRNAs miR-145, miR-143, and miR-200b in synchronous and metachronous multiple meningiomas. Real-time PCR was used for expression analysis. In our study, we observed a statistical difference only for miR-145 between the metachronous and synchronous groups, indicating hypoexpression of miR-145 in the metachronous group (p = 0.03). In the ROC curve analysis, miR-145 demonstrated better performance in distinguishing metachronous cases from controls, with an AUC of 81%, sensitivity of 93%, and specificity of 60%. Our results suggest that miR-145 has potential as a tumor marker associated with the pluripotency axis in multiple meningiomas, and further studies are needed to clarify the roles of miR-143 and miR-200b in multiple meningiomas.
Abualnaja, S.Y., Morris, J.S., Rashid, H., Cook, W.H. and Helmy, A.E. (2024) Machine Learning for Predicting Post-Operative Outcomes in Meningiomas: A Systematic Review and Meta-Analysis. Acta Neurochirurgica , 166, Article No. 505. https://doi.org/10.1007/s00701-024-06344-z
Fahlström, A., Dwivedi, S. and Drummond, K. (2023) Multiple Meningiomas: Epidemiology, Management, and Outcomes. Neuro - Oncology Advances , 5, i35-i48. https://doi.org/10.1093/noajnl/vdac108
Olson, J., Reddy, D. and Cai, D.X. (2025) Multiple Meningiomas of Different Variants in a Single Patient: Illustrative Cases. Journal of Neurosurgery : Case Less ons , 9, CASE24359. https://doi.org/10.3171/case24359
Terrier, L.M. and François, P. (2016) Méningiomes Multiples. Neurochirurgie , 62, 128-135. https://doi.org/10.1016/j.neuchi.2015.12.006
Tsermoulas, G., Turel, M.K., Wilcox, J.T., Shultz, D., Farb, R., Zadeh, G., et al . (2018) Management of Multiple Meningiomas. Journal of Neurosurgery , 128, 1403-1409. https://doi.org/10.3171/2017.2.jns162608
Wang, J.Z., Landry, A.P., Raleigh, D.R., Sahm, F., Walsh, K.M., Goldbrunner, R., et a l . (2024) Meningioma: International Consortium on Meningiomas Consensus Review on Scientific Advances and Treatment Paradigms for Clinicians, Researchers, and Patients. Neuro - Oncology , 26, 1742-1780. https://doi.org/10.1093/neuonc/noae082
Franca, R.A., Della Monica, R., Corvino, S., Chiariotti, L. and Del Basso De Caro, M. (2023) WHO Grade and Pathological Markers of Meningiomas: Clinical and Prognostic Role. Pathology — Research and Practice , 243, Article ID: 154340. https://doi.org/10.1016/j.prp.2023.154340
Boetto, J., Birzu, C., Kalamarides, M., Peyre, M. and Sanson, M. (2022) Les méningiomes: Mise au point sur les connaissances actuelles. La Revue de Médecine Interne , 43, 98-105. https://doi.org/10.1016/j.revmed.2021.06.011
Araújo Pereira, B.J., Nogueira de Almeida, A., Pires de Aguiar, P.H., Paiva, W.S., Teixeira, M.J. and Nagahashi Marie, S.K. (2019) Multiple Intracranial Meningiomas: A Case Series and Review of the Literature. World Neurosurgery , 122, e1536-e1541. https://doi.org/10.1016/j.wneu.2018.11.097
Di Bonaventura, R., Martini, M., Cenci, T., Caccavella, V.M., Barresi, V., Gessi, M., et al . (2022) Dissecting Stemness in Aggressive Intracranial Meningiomas: Prognostic Role of SOX2 Expression. International Journal of Molecular Sciences , 23, Article No. 11690. https://doi.org/10.3390/ijms231911690
Sell, S. (2010) On the Stem Cell Origin of Cancer. The American Journal of Pathology , 176, 2584-2594. https://doi.org/10.2353/ajpath.2010.091064
Ma, Q., Long, W., Xing, C., Chu, J., Luo, M., Wang, H.Y., et al . (2018) Cancer Stem Cells and Immunosuppressive Microenvironment in Glioma. Frontiers in Immunology , 9, Article 2924. https://doi.org/10.3389/fimmu.2018.02924
Yang, L., Shi, P., Zhao, G., Xu, J., Peng, W., Zhang, J., et al . (2020) Targeting Cancer Stem Cell Pathways for Cancer Therapy. Signal Transduction and Targeted Therapy , 5, Article No. 8. https://doi.org/10.1038/s41392-020-0110-5
Liu, A., Yu, X. and Liu, S. (2013) Pluripotency Transcription Factors and Cancer Stem Cells: Small Genes Make a Big Difference. Chinese Journal of Cancer , 32, 483-487. https://doi.org/10.5732/cjc.012.10282
Voutsadakis, I.A. (2015) Pluripotency Transcription Factors in the Pathogenesis of Colorectal Cancer and Implications for Prognosis. Biomarkers in Medicine , 9, 349-361. https://doi.org/10.2217/bmm.15.4
Mohiuddin, I.S., Wei, S.-J. and Kang, M.H. (2019) Role of OCT4 in Cancer Stem-Like Cells and Chemotherapy Resistance. Biochimica et Biophysica Acta . Molecular Basis of Disease , 1866, Article ID: 165432.
Braga, T.V., Evangelista, F.C.G., Gomes, L.C., Araújo, S.S.d.S., Carvalho, M.d.G. and Sabino, A.d.P. (2017) Evaluation of Mir-15a and Mir-16-1 as Prognostic Biomarkers in Chronic Lymphocytic Leukemia. Biomedicine & Pharmacotherapy , 92, 864-869. https://doi.org/10.1016/j.biopha.2017.05.144
Mirzaei, S., Zarrabi, A., Asnaf, S.E., Hashemi, F., Zabolian, A., Hushmandi, K., et al . (2021) The Role of MicroRNA-338-3p in Cancer: Growth, Invasion, Chemoresistance, and Mediators. Life Sciences , 268, Article ID: 119005. https://doi.org/10.1016/j.lfs.2020.119005
Morgado, A.L., Rodrigues, C.M.P. and Solá, S. (2016) MicroRNA-145 Regulates Neural Stem Cell Differentiation through the SOX2-Lin28/Let-7 Signaling Pathway. Stem Cells , 34, 1386-1395. https://doi.org/10.1002/stem.2309
Zhou, X., Yue, Y., Wang, R., Gong, B. and Duan, Z. (2017) MicroRNA-145 Inhibits Tumorigenesis and Invasion of Cervical Cancer Stem Cells. International Journal of Oncology , 50, 853-862. https://doi.org/10.3892/ijo.2017.3857
Zhao, H., Bi, M., Lou, M., Yang, X. and Sun, L. (2021) Downregulation of SOX2-OT Prevents Hepatocellular Carcinoma Progression through miR-143-3p/MSI2. Fron tiers in Oncology , 11, Article 685912. https://doi.org/10.3389/fonc.2021.685912
Wang, B., Li, M., Wu, Z., Li, X., Li, Y., Shi, X., et al . (2015) Associations between SOX2 and Mir-200b Expression with the Clinicopathological Characteristics and Prognosis of Patients with Glioma. Experimental and Therapeutic Medicine , 10, 88-96. https://doi.org/10.3892/etm.2015.2488
Ishi, Y., Era, T., Yuzawa, S., Okamoto, M., Sawaya, R., Motegi, H., et al . (2022) Analysis of Induced Pluripotent Stem Cell Clones Derived from a Patient with Mosaic Neurofibromatosis Type 2. American Journal of Medical Genetics Part A , 188, 1863-1867. https://doi.org/10.1002/ajmg.a.62700
Erson-Omay, E.Z., Vetsa, S., Vasandani, S., Barak, T., Nadar, A., Marianayagam, N.J., et al . (2022) Correction: Genomic Profiling of Sporadic Multiple Meningiomas. BMC Medical Genomics , 15, Article No. 112. https://doi.org/10.1186/s12920-022-01273-1
Kopf, L., Warneke, N., Grauer, O., Thomas, C., Hess, K., Schwake, M., et al . (2023) Prognosis and Histology of Sporadic Synchronous and Metachronous Meningiomas and Comparative Analyses with Singular Lesions. Neurosurgical Review , 46, Article No. 55. https://doi.org/10.1007/s10143-023-01958-w
Juratli, T.A., Prilop, I., Saalfeld, F.C., Herold, S., Meinhardt, M., Wenzel, C., et al . (2021) Sporadic Multiple Meningiomas Harbor Distinct Driver Mutations. Acta Neuropathologica Communications , 9, Article No. 8. https://doi.org/10.1186/s40478-020-01113-2
Zuniga, R.D.d.R., Carrijo, G.S., do Vale, M.R., Reis, B.d.C.A.A., da Veiga, G.R.L., de Aguiar, P.H.P., et al . (2025) Pathogenic Variants and Prognosis in Meningiomas: A Systematic Review and Meta-Analysis. World Neurosurgery , 198, Article ID: 123988. https://doi.org/10.1016/j.wneu.2025.123988
Slavik, H., Balik, V., Vrbkova, J., Rehulkova, A., Vaverka, M., Hrabalek, L., et al . (2020) Identification of Meningioma Patients at High Risk of Tumor Recurrence Using MicroRNA Profiling. Neurosurgery , 87, 1055-1063. https://doi.org/10.1093/neuros/nyaa009
Schoenhals, M., Kassambara, A., Vos, J.D., Hose, D., Moreaux, J. and Klein, B. (2009) Embryonic Stem Cell Markers Expression in Cancers. Biochemical and Biophysical Research Communications , 383, 157-162. https://doi.org/10.1016/j.bbrc.2009.02.156
Mamun, M.A., Mannoor, K., Cao, J., Qadri, F. and Song, X. (2018) SOX2 in Cancer Stemness: Tumor Malignancy and Therapeutic Potentials. Journal of Molecular Cell Biology , 12, 85-98. https://doi.org/10.1093/jmcb/mjy080
Feng, R. and Wen, J. (2015) Overview of the Roles of SOX2 in Stem Cell and Development. Biological Chemistry , 396, 883-891. https://doi.org/10.1515/hsz-2014-0317
Lin, Y., Ge, X., Wen, Y., Shi, Z., Chen, Q., Wang, M., et al . (2016) MiRNA-145 Increases Therapeutic Sensibility to Gemcitabine Treatment of Pancreatic Adenocarcinoma Cells. Oncotarget , 7, 70857-70868. https://doi.org/10.18632/oncotarget.12268
Gao, Y., Zhang, Z., Li, K., Gong, L., Yang, Q., Huang, X., et al . (2017) Linc-DYNC2H1-4 Promotes EMT and CSC Phenotypes by Acting as a Sponge of Mir-145 in Pancreatic Cancer Cells. Cell Death & Disease , 8, e2924. https://doi.org/10.1038/cddis.2017.311
Tang, W., Zhang, X., Tan, W., Gao, J., Pan, L., Ye, X., et al . (2019) miR-145-5p Suppresses Breast Cancer Progression by Inhibiting SOX2. Journal of Surgical Research , 236, 278-287. https://doi.org/10.1016/j.jss.2018.11.030
Ngalame, N.N.O., Makia, N.L., Waalkes, M.P. and Tokar, E.J. (2016) Mitigation of Arsenic-Induced Acquired Cancer Phenotype in Prostate Cancer Stem Cells by miR-143 Restoration. Toxicology and Applied Pharmacology , 312, 11-18. https://doi.org/10.1016/j.taap.2015.12.013
Xie, F., Li, C., Zhang, X., Peng, W. and Wen, T. (2019) MiR-143-3p Suppresses Tumorigenesis in Pancreatic Ductal Adenocarcinoma by Targeting KRAS. Biomedicine & Pharmacotherapy , 119, Article ID: 109424. https://doi.org/10.1016/j.biopha.2019.109424
Huang, S., Guo, W., Tang, Y., Ren, D., Zou, X. and Peng, X. (2012) miR-143 and miR-145 Inhibit Stem Cell Characteristics of PC-3 Prostate Cancer Cells. Oncology Rep orts , 28, 1831-1837. https://doi.org/10.3892/or.2012.2015
Xiao, W., Li, Y., Zeng, C., Tu, M., Jiang, W., Dai, Z., et al . (2016) MicroRNA-200b Acts as a Tumor Suppressor in Osteosarcoma via Targeting ZEB1. OncoTargets and Therapy , 9, 3101-3111. https://doi.org/10.2147/ott.s96561
Zhang, J., Gao, Y., Yu, M., Wu, H., Ai, Z., Wu, Y., et al . (2015) Retinoic Acid Induces Embryonic Stem Cell Differentiation by Altering both Encoding RNA and MicroRNA Expression. PLOS ONE , 10, e0132566. https://doi.org/10.1371/journal.pone.0132566
Yao, Y., Hu, J., Shen, Z., Yao, R., Liu, S., Li, Y., et al . (2015) MiR-200b Expression in Breast Cancer: A Prognostic Marker and Act on Cell Proliferation and Apoptosis by Targeting Sp1. Journal of Cellular and Molecular Medicine , 19, 760-769. https://doi.org/10.1111/jcmm.12432