Circular RNA cFAM210A, degradable by HBx, inhibits HCC tumorigenesis by suppressing YBX1 transactivation

Abstract

Hepatitis B protein x (HBx) has been reported to promote tumorigenesis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), but the mechanism awaits further investigation. In this study, we found that cFAM210A (a circular RNA derived from the third exon of transcript NM_001098801 of the FAM210A gene; CircBase ID: hsa_circ_0003979) can be silenced by HBx. cFAM210A expression was downregulated and negatively correlated with tumorigenesis in patients with HBV-related HCC. Furthermore, cFAM210A reduced the proliferation, stemness, and tumorigenicity of HCC cells. Mechanistically, HBx increased the N6-methyladenosine (m6A) level of cFAM210A by promoting the expression of RBM15 (an m6A methyltransferase), thus inducing the degradation of cFAM210A via the YTHDF2-HRSP12-RNase P/MRP pathway. cFAM210A bound to YBX1 and inhibited its phosphorylation, suppressing its transactivation function toward MET. These findings suggest the important role of circular RNAs in HBx-induced hepatocarcinogenesis and identify cFAM210A a potential target in the prevention and treatment of HBV-related HCC.

Circular RNA cFAM210A: a new hope in HBV-related HCC treatment

A study has identified a circular RNA, cFAM210A, that inhibits the growth and stemness of hepatocellular carcinoma (HCC) cells. Researchers found that the hepatitis B virus (HBV) protein HBx promotes the degradation of cFAM210A through a process called N6-methyladenosine modification. This leads to increased tumour growth and stemness in HCC cells. By inhibiting the transactivation function of a protein called YBX1 on another protein called MET, cFAM210A suppresses tumour progression. These findings highlight the potential of cFAM210A as a target for the prevention and treatment of HBV-related HCC.