Epigenetic Associations between lncRNA/circRNA and miRNA in Hepatocellular Carcinoma

SIMPLE SUMMARY: Non-coding RNAs such as microRNAs, long non-coding RNAs, and circular RNAs contribute to the development and progression of hepatocellular carcinoma through epigenetic association. Long non-coding RNAs and circular RNAs act as competing endogenous RNAs that contain binding sites for miRNAs and thus compete with the miRNAs, which results in promotion of miRNA target gene expression, thereby leading to proliferation and metastasis of hepatocellular carcinoma. Competing endogenous RNAs have the potential to become diagnostic biomarkers and therapeutic targets for treatment of hepatocellular carcinoma. ABSTRACT: The three major members of non-coding RNAs (ncRNAs), named microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play an important role in hepatocellular carcinoma (HCC) development. Recently, the competing endogenous RNA (ceRNA) regulation model described lncRNA/circRNA as a sponge for miRNAs to indirectly regulate miRNA downstream target genes. Accumulating evidence has indicated that ceRNA regulatory networks are associated with biological processes in HCC, including cancer cell growth, epithelial to mesenchymal transition (EMT), metastasis, and chemoresistance. In this review, we summarize recent discoveries, which are specific ceRNA regulatory networks (lncRNA/circRNA-miRNA-mRNA) in HCC and discuss their clinical significance.