Circular RNA as An Epigenetic Regulator in Chronic Liver Diseases

Abstract

Circular RNA (circRNA) is a type of non-coding RNA characterized by a covalently closed continuous loop. CircRNA is generated by pre-mRNA through back-splicing and is probably cleared up by extracellular vesicles. CircRNAs play a pivotal role in the epigenetic regulation of gene expression at transcriptional and post-transcriptional levels. Recently, circRNAs have been demonstrated to be involved in the regulation of liver homeostasis and diseases. However, the epigenetic role and underlying mechanisms of circRNAs in chronic liver diseases remain unclear. This review discussed the role of circRNAs in non-neoplastic chronic liver diseases, including alcoholic liver disease (ALD), metabolic-associated fatty liver disease (MAFLD), viral hepatitis, liver injury and regeneration, liver cirrhosis, and autoimmune liver disease. The review also highlighted that further efforts are urgently needed to develop circRNAs as novel diagnostics and therapeutics for chronic liver diseases.

Nonalcoholic Fatty Liver Disease (NAFLD): Pathogenesis and Noninvasive Diagnosis

“…Circular RNAs (circRNAs) are large ncRNAs that do not encode for functional proteins and are the products of the transcription process, though circRNAs are derived from the back-splicing events [ 199 , 200 , 201 ]. This back-splicing process produces covalently closed loop RNAs that contain either exons or introns or mixtures of both, with no 5′-cap or 3′-tail [ 199 , 200 , 201 ].…”

“…Circular RNAs (circRNAs) are large ncRNAs that do not encode for functional proteins and are the products of the transcription process, though circRNAs are derived from the back-splicing events [ 199 , 200 , 201 ]. This back-splicing process produces covalently closed loop RNAs that contain either exons or introns or mixtures of both, with no 5′-cap or 3′-tail [ 199 , 200 , 201 ]. Like lncRNAs, circRNAs also cis- and transregulate target molecules with similar mechanisms, such as miRNA sponges and protein decoys, but have additional regulatory roles towards parental genes [ 199 , 200 , 201 ].…”

“…This back-splicing process produces covalently closed loop RNAs that contain either exons or introns or mixtures of both, with no 5′-cap or 3′-tail [ 199 , 200 , 201 ]. Like lncRNAs, circRNAs also cis- and transregulate target molecules with similar mechanisms, such as miRNA sponges and protein decoys, but have additional regulatory roles towards parental genes [ 199 , 200 , 201 ].…”

The Emerging Roles of Circular RNAs in the Chemoresistance of Gastrointestinal Cancer

“…Reportedly, chemoresistant cancers exhibited alleviated epigenetic inhibition of MDR1 through promoter hypomethylation and histone acetylation (Sharma et al, 2010;Toth et al, 2012). CircRNAs play a critical role in the epigenetic modulation of gene expression (Zeng et al, 2021). It is intriguing whether circRNAs drive the epigenetic alteration of efflux pump genes.…”

Mechanism and Therapeutic Opportunities of Histone Modifications in Chronic Liver Disease

“…The incidence and prevalence rates of CLD are rising worldwide ( Liangpunsakul et al, 2016 ; Wong et al, 2019 ; Younossi, 2019 ; Moon et al, 2020 ), resulting in a high rate of disability and increased health care utilization ( Moon et al, 2020 ). The etiologies of CLD comprise chronic Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infection, metabolic syndrome, excessive alcohol consumption, exposure to the chemical compound, autoimmune response, etc ., ( Zeng et al, 2021 ). These etiologies contribute to chronic liver damages, which can progress to liver fibrosis, liver cirrhosis, and even hepatocellular carcinoma (HCC) ( Hardy and Mann, 2016 ), further reducing the life quality of patients.…”