N 6 ‐methyladenosine modification of circular RNA circ‐ARL3 facilitates Hepatitis B virus ‐associated hepatocellular carcinoma via sponging miR ‐1305

作者：Xi Rao, Lingling Lai, Xiaopeng Li, Liang Wang, Li Ai, Qian Yang · 发表于：IUBMB Life · 年份：2020 · DOI：10.1002/iub.2438 · 被引用次数：97 · 研究领域：Circular RNAs in diseases、MicroRNA in disease regulation、RNA modifications and cancer

Abstract Hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC), whether circular RNA (circRNA) is involved in this process remains unknown. In this study, we performed circRNA microarray profile and found an HBV‐related circRNA, circ‐ARL3 (hsa_circ_0092493). Stable knockdown of circ‐ARL3 inhibited the proliferation and invasion of HBV + HCC cells. High circ‐ARL3 was positively correlated with malignant clinical features and poor prognosis. In terms of mechanism, HBx protein upregulated N 6 ‐methyladenosine (m 6 A) methyltransferases METTL3 expression, increasing the m 6 A modification of circ‐ARL3; then, m 6 A reader YTHDC1 bound to m 6 A‐modified of circ‐ARL3 and favored its reverse splicing and biogenesis. Furthermore, circ‐ARL3 was able to sponge miR‐1305, antagonizing the inhibitory effects of miR‐1305 on a cohort of target oncogenes, thereby promoting HBV + HCC progression. Importantly, depletion of circ‐ARL3 significantly retarded HBV + HCC cell growth in vivo, whereas this effect was evidently blocked after silencing of miR‐1305. Collectively, our data suggest that circ‐ARL3 is a critical regulator in HBV‐related HCC, targeting the axis of circ‐ARL3/miR‐1305 may be a promising treatment for HBV + HCC patients.