Circular RNAs in Hepatocellular Carcinoma: Emerging Functions to Clinical Significances.

Yucheng Zhang,Yali Wang

doi:10.3389/fonc.2021.667428

Abstract

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver and carries high morbidity and mortality. Diagnosing HCC at an early stage is challenging. Therefore, finding new, highly sensitive and specific diagnostic biomarkers for the diagnosis and prognosis of HCC patients is extremely important. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently closed loop structures. They are characterized by remarkable stability, long half-life, abundance and evolutionary conservation. Recent studies have shown that many circRNAs are expressed aberrantly in HCC tissues and have important regulatory roles during the development and progression of HCC. Hence, circRNAs are promising biomarkers for the diagnosis and prognosis of HCC. This review: (i) summarizes the biogenesis, categories, and functions of circRNAs; (ii) focuses on current progress of dysregulated expression of circRNAs in HCC with regard to regulation of the tumor hallmarks, “stemness” of cancer cells, and immunotherapy; (iii) highlights circRNAs as potential biomarkers and therapeutic targets for HCC; and (iv) discusses some of the challenges, questions and future perspectives of circRNAs research in HCC.

Highlights

Hepatocellular carcinoma (HCC) is the fourth-leading cause of cancer-related death overall worldwide, and the fastest-growing cause of cancer-related deaths in the United States [1, 2]
Accumulating evidence has demonstrated that some circular RNAs are involved in HCC carcinogenesis and progression, including proliferation, angiogenesis, apoptosis, invasion and migration. circRNAs are a novel type of noncodingRNAs and harbor a covalently closed loop structure with neither 5′ to 3′ polarity nor a polyadenylated tail [6]
Analyses of the expression profile of circRNAs using RNA sequencing or microarray technology has shown that some dysregulated circRNAs have important roles in HCC

Summary

Introduction

Hepatocellular carcinoma (HCC) is the fourth-leading cause of cancer-related death overall worldwide, and the fastest-growing cause of cancer-related deaths in the United States [1, 2]. Several studies have revealed five major functions of circRNAs: binding to RBPs and serving protein scaffolds; sponging miRNAs to regulate target genes; encoding peptides or proteins; promoting transcription of parental genes; regulating alternative splicing. Mitogenic signals activate cyclin D/CDK4/ 6 by phosphorylating retinoblastoma (RB) tumor-suppressor protein, which inhibits the activity of E2F transcription factors, and drives the expression of E2F target genes and promotes cell cycle progression [65, 66].

Results

Conclusion