Role of m6A RNA methylation in the development of hepatitis B virus‐associated hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the most common liver malignancy that can be developed from hepatitis B and cirrhosis. Many pathophysiological alterations, including hepatitis B virus (HBV) DNA integration, oxidative stress, cytokine release, telomerase homeostasis, mitochondrial damage, epigenetic modification, and tumor microenvironment, are involved in the biological process from hepatitis B to cirrhosis and HCC. N6-methyladenosine (m6A), as an epitranscriptomic modification of RNAs, can regulate the stability, splicing, degradation, transcription, and translation of downstream target RNAs in HBV and liver cancer cells. m6A regulators (writers, erasers, and readers) play an important role in the pathogenesis of HBV-associated HCC by regulating cell proliferation, apoptosis, migration, autophagy, differentiation, inflammation, angiogenesis, and tumor microenvironment. This review summarizes the current progress of m6A methylation in the molecular mechanisms, biological functions, and potential clinical implications of HBV-associated HCC.declare no conflict of interest. Author contribution: CZ drafted the manuscript and constructed the figures. DD and WZ revised the manuscript and constructed the tables. WY and YG revised the manuscript. QW managed the article design, reviewed the manuscript, and provided funding support. All authors contributed to the article and approved the submitted version.

Molecular questioning of potential efficacy of epsilon targeted antiviral treatment option for Domestic Cat Hepadnavirus

“…Based on these studies, m6A expression levels can cause bilateral effects. However, m6A is known to play a regulatory role in many biological activities such as immune response, tumourigenesis, and viral replication [33][34][35]. When we compared the stem-loop structure of DCH and HBV epsilon by secondary structure analysis, we found that they have almost the same conformation on the X protein, although the nucleotide spacing is different.…”

“…Recent literature suggests that N6-methyladenosine (m6A) modi cation may play an important role in the regulation of the hepadnaviral life cycle [33][34][35]. As the most abundant epitranscriptomic internal modi cation factor, m6A can be expressed by cellular or viral RNAs.…”

Liver-specific Mettl14 deletion induces nuclear heterotypia and dysregulates RNA export machinery

“…Chronic HBV infection is a major cause of liver fibrosis and progression to hepatocellular carcinoma (49). Given the known role of both m 6 A and HBV in HCC development and progression, and the known role of m 6 A on HBV replication cycle and protein translation, we were interested in whether disruption of m 6 A modification in Mettl14 [fl/fl] /Alb-Cre mice would impact outcomes of HBV exposure (15,(50)(51)(52).…”

Clinical significance of RNA methylation in hepatocellular carcinoma

“…Increasing evidence indicates that RNA methylation plays a crucial role in tumorigenesis, and dysregulation of RNA methylation has been observed in various cancers including HCC [ 60 – 64 ]. Elucidating the multifaceted mechanisms of RNA modifications in the genetic pathogenesis of HCC is increasingly getting considered as a valuable direction for the clinical management of HCC [ 40 , 65 , 66 ].…”