An Integrated Analysis of Aberrantly Expressed miRNA and mRNA Profiles Unveils a Robust Regulatory Network in HepG2 Cell

Abstract

As crucial negative regulatory small non-coding molecules, microRNAs (miRNAs), have multiple biological roles. The abnormal expression of specific miRNAs may contribute to the occurrence and development of tumor. Here, based on HepG2 and L02 cells, we attempted to demonstrate the potential regulatory network of aberrantly expressed miRNA profiles, interaction between miRNA and mRNA, and potential functional correlation between different miRNAs. De-regulated miRNA and mRNA expression profiles were completely surveyed and identified by applying deep sequenc-ing and microarray techniques, respectively. The genome-wide and integrative analysis of miRNA-mRNA was performed based on their functional relationship according to experimentally validated and predicted targets. Nearly 50% targets were negatively regulated by at least 2 aberrantly expressed miRNAs. Similar results were obtained based on experimentally validated and predicted targets. Compared with abnormal miRNAs, their targets showed various expression patterns: stably expressed, down-regulated or up-regulated. Although the theoretical potential miRNA-mRNA interaction could be predicted, they showed consistent or inconsistent expression patterns. Both functional enrichment analysis of target mRNAs of dysregulated miRNAs and abnormal mRNA profiles suggested that corresponding pathways were involved in tumorigenesis. Moreover, to obtain potential functional relationships between different miRNAs, we also performed expression analysis of homologous miRNAs in gene families. Generally, they could co-regulate biological processes with similar roles. The integrative analysis of miRNA-mRNA indicated a complex and flexible regulatory network. The robust network mainly derived from multiple targets for a specific miRNA (and vice versa), each mRNA and co-regulation roles of different miRNAs.