Circular RNA As a Novel Biomarker and Therapeutic Target for HCC

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2022 Jun 24

PMID 35741077

Authors

Hongwu Meng

Ruowen Niu

Cheng Huang

Jun Li

Affiliations

Soon will be listed here.

Abstract

Circular RNA (circRNA) is a kind of endogenous non-coding RNA (ncRNA), which is produced by the reverse splicing of precursor mRNA (pre mRNA). It is widely expressed in a variety of biological cells. Due to the special formation mode, circRNA does not have a 5' terminal cap and 3' poly (A) tail structure. Compared with linear RNA, circRNA is more stable to exonuclease and ribonuclease. In addition, circRNA is structurally conserved, has a stable sequence and is tissue-specific. With the development of high-throughput sequencing and bioinformatics technology, more and more circRNAs have been found. CircRNA plays an important pathophysiological role in the occurrence and development of alcoholic liver injury (ALI), hepatic fibrosis (HF), hepatocellular carcinoma (HCC), and other liver diseases. Our group has been committed to the research of liver disease diagnosis and treatment targets. We review the function and mechanism of circRNA in ALI, HF and HCC, expecting to provide new ideas for the diagnosis, treatment, and prognosis of liver diseases.

Citing Articles

Circular RNA Vav3 mediated ALV-J inhibition of autophagy by modulating the gga-miR-375/CIP2A axis and activating AKT.

Chen L, Xu H, Liu R, Yao Z, Xie Q, Zhang X Poult Sci. 2025; 104(4):104923.

PMID: 39987600 PMC: 11904538. DOI: 10.1016/j.psj.2025.104923.

CircRNA circACTN4 Promotes the Progression of Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma by Targeting the miR-424-5p/NCAPG/Wnt Axis.

Shan J, Pu J, Chen X, Zhang Y, Li J, Qin L Clin Exp Med. 2025; 25(1):47.

PMID: 39891781 PMC: 11787268. DOI: 10.1007/s10238-025-01573-7.

Circ_0001944 Targets the miR-1292-5p/FBLN2 Axis to Facilitate Sorafenib Resistance in Hepatocellular Carcinoma by Impeding Ferroptosis.

Jing F, Shi Y, Jiang D, Li X, Sun J, Guo Q Immunotargets Ther. 2024; 13:643-659.

PMID: 39624827 PMC: 11611519. DOI: 10.2147/ITT.S463556.

Identification and Validation of the Hsa_circ_0001726/miR-140-3p/KRAS Axis in Hepatocellular Carcinoma Based on Microarray Analyses and Experiments.

Chi X, Chen Z, Yu J, Xie X, Lin Z, Chen Y J Clin Transl Hepatol. 2024; 12(11):897-906.

PMID: 39544243 PMC: 11557365. DOI: 10.14218/JCTH.2024.00270.

N-methyladenosine modification of circular RNA circASH2L suppresses growth and metastasis in hepatocellular carcinoma through regulating hsa-miR-525-3p/MTUS2 axis.

Xu D, Liu Y, Liu Q, Li G, Zhang L, Yu C J Transl Med. 2024; 22(1):1026.

PMID: 39543614 PMC: 11566831. DOI: 10.1186/s12967-024-05745-z.

References

Chen X, Li W, Chen Y, Li X, Li H, Huang H . Suppression of SUN2 by DNA methylation is associated with HSCs activation and hepatic fibrosis. Cell Death Dis. 2018; 9(10):1021. PMC: 6170444. DOI: 10.1038/s41419-018-1032-9. View

Guo X, Chen J, Sun F, Wang Y, Pan Q, Fan J . circRNA_0046367 Prevents Hepatoxicity of Lipid Peroxidation: An Inhibitory Role against Hepatic Steatosis. Oxid Med Cell Longev. 2017; 2017:3960197. PMC: 5605923. DOI: 10.1155/2017/3960197. View

Guan Z, Tan J, Gao W, Li X, Yang Y, Li X . Circular RNA hsa_circ_0016788 regulates hepatocellular carcinoma tumorigenesis through miR-486/CDK4 pathway. J Cell Physiol. 2018; 234(1):500-508. DOI: 10.1002/jcp.26612. View

Chen G, Shi Y, Liu M, Sun J . circHIPK3 regulates cell proliferation and migration by sponging miR-124 and regulating AQP3 expression in hepatocellular carcinoma. Cell Death Dis. 2018; 9(2):175. PMC: 5833724. DOI: 10.1038/s41419-017-0204-3. View

Ji D, Chen G, Wang J, Ji S, Wu X, Lu X . Hsa_circ_0070963 inhibits liver fibrosis via regulation of miR-223-3p and LEMD3. Aging (Albany NY). 2020; 12(2):1643-1655. PMC: 7053641. DOI: 10.18632/aging.102705. View

Jeck W, Sorrentino J, Wang K, Slevin M, Burd C, Liu J . Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA. 2012; 19(2):141-57. PMC: 3543092. DOI: 10.1261/rna.035667.112. View

Meng H, Wang L, You H, Huang C, Li J . Circular RNA expression profile of liver tissues in an EtOH-induced mouse model of alcoholic hepatitis. Eur J Pharmacol. 2019; 862:172642. DOI: 10.1016/j.ejphar.2019.172642. View

Li S, Weng J, Song F, Li L, Xiao C, Yang W . Circular RNA circZNF566 promotes hepatocellular carcinoma progression by sponging miR-4738-3p and regulating TDO2 expression. Cell Death Dis. 2020; 11(6):452. PMC: 7293356. DOI: 10.1038/s41419-020-2616-8. View

Lin Q, Ling Y, Chen J, Zhou C, Chen J, Li X . Circular RNA circCDK13 suppresses cell proliferation, migration and invasion by modulating the JAK/STAT and PI3K/AKT pathways in liver cancer. Int J Oncol. 2018; 53(1):246-256. DOI: 10.3892/ijo.2018.4371. View

10.

Bai N, Peng E, Qiu X, Lyu N, Zhang Z, Tao Y . circFBLIM1 act as a ceRNA to promote hepatocellular cancer progression by sponging miR-346. J Exp Clin Cancer Res. 2018; 37(1):172. PMC: 6062991. DOI: 10.1186/s13046-018-0838-8. View

11.

Wang M, Yu F, Li P . Circular RNAs: Characteristics, Function and Clinical Significance in Hepatocellular Carcinoma. Cancers (Basel). 2018; 10(8). PMC: 6116001. DOI: 10.3390/cancers10080258. View

12.

Niu W, Chen L, Zhang P, Zang H, Zhu B, Shao W . Circ_0091579 promotes proliferative ability and metastasis of liver cancer cells by regulating microRNA-490-3p. Eur Rev Med Pharmacol Sci. 2019; 23(23):10264-10273. DOI: 10.26355/eurrev_201912_19664. View

13.

Wang Y, Wang Z . Efficient backsplicing produces translatable circular mRNAs. RNA. 2014; 21(2):172-9. PMC: 4338345. DOI: 10.1261/rna.048272.114. View

14.

Wang F, Fan J, Zhang Z, Gao B, Wang H . The global burden of liver disease: the major impact of China. Hepatology. 2014; 60(6):2099-108. PMC: 4867229. DOI: 10.1002/hep.27406. View

15.

Li X, Shen M . Circular RNA hsa_circ_103809 suppresses hepatocellular carcinoma proliferation and invasion by sponging miR-620. Eur Rev Med Pharmacol Sci. 2019; 23(2):555-566. DOI: 10.26355/eurrev_201902_16868. View

16.

Legnini I, Di Timoteo G, Rossi F, Morlando M, Briganti F, Sthandier O . Circ-ZNF609 Is a Circular RNA that Can Be Translated and Functions in Myogenesis. Mol Cell. 2017; 66(1):22-37.e9. PMC: 5387670. DOI: 10.1016/j.molcel.2017.02.017. View

17.

Liu W, Feng R, Li X, Li D, Zhai W . TGF-β- and lipopolysaccharide-induced upregulation of circular RNA PWWP2A promotes hepatic fibrosis via sponging miR-203 and miR-223. Aging (Albany NY). 2019; 11(21):9569-9580. PMC: 6874441. DOI: 10.18632/aging.102405. View

18.

Qiu L, Huang Y, Li Z, Dong X, Chen G, Xu H . Circular RNA profiling identifies circADAMTS13 as a miR-484 sponge which suppresses cell proliferation in hepatocellular carcinoma. Mol Oncol. 2018; 13(2):441-455. PMC: 6360375. DOI: 10.1002/1878-0261.12424. View

19.

Chen Y, Chen R, Ahmad S, Verma R, Kasturi S, Amaya L . N6-Methyladenosine Modification Controls Circular RNA Immunity. Mol Cell. 2019; 76(1):96-109.e9. PMC: 6778039. DOI: 10.1016/j.molcel.2019.07.016. View

20.

Su Y, Lv X, Yin W, Zhou L, Hu Y, Zhou A . CircRNA Cdr1as functions as a competitive endogenous RNA to promote hepatocellular carcinoma progression. Aging (Albany NY). 2019; 11(19):8183-8203. PMC: 6814590. DOI: 10.18632/aging.102312. View