Epigenetic Associations between lncRNA/circRNA and miRNA in Hepatocellular Carcinoma.

Tae-Su Han,Hyun Seung Ban,Keun Hur,Hyun-Soo Cho

doi:10.3390/cancers12092622

Tae-Su Han, Hyun Seung Ban + Show 2 more

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https://doi.org/10.3390/cancers12092622

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Abstract

Simple SummaryNon-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.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.

Highlights

Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers and highly lethal malignancies
CeRNA network network between between oncology. In in this this review, review, we we introduce introduce the mechanism mechanism of long non-coding RNAs (lncRNAs)/circRNAs lncRNA/circRNAsand andmiRNAs miRNAsand anddiscuss discuss its its possible possible role role in HCC progression
Based on high-throughput RNA-sequencing and analysis with CIRI (V2.0) software [138,139], 1,717 and 582 differentially expressed circRNAs were identified in sorafenib-resistant Huh7-S and HepG2-S HCC cells compared to parental HCC cells, respectively

Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers and highly lethal malignancies. Ebert et al observed similar phenomena: artificial overexpression of miRNA binding sites leads to upregulation of miRNA targets acting as RNA sponges [51]. LncRNA MALAT1 sponged miR-146b-5p to induce TRAF6 expression leading to HCC metastasis [62]. The lncRNA FLVCR1-AS1 sponged miR-513c to modulate HCC metastasis and proliferation via up-regulation of MET expression [67]. Overexpression of lncRNA ROR induced ZEB2 expression by sponging miR-145, and increased EMT and HCC metastasis [68]. The lncRNA MIAT sponged miR-520d-3p, upregulating EPHA2 expression leading to HCC proliferation and metastasis [81]. Overall, overexpressed lncRNAs are critically involved in HCC proliferation and metastasis via regulation of the cell cycle, autophagy, apoptosis, and several signaling pathways. Overexpressed lncRNAs are recognized as HCC biomarkers and therapeutic targets

Tumor Suppressor lncRNAs Inhibit HCC Tumorigenesis by Sponging Onco-miRNAs

Circular RNA and microRNA Networks in HCC

Tumor Suppressor Circrnas Inhibit HCC Tumorigenesis by Sponging Onco-miRNAs

Clinical Application of lncRNAs and CircRNAs as Novel Biomarkers in HCC

Conclusions