N6 ‐methyladenosine modification of circular RNA circ‐ARL3 facilitates Hepatitis B virus‐associated hepatocellular carcinoma via sponging miR‐1305

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 N6‐methyladenosine (m6A) methyltransferases METTL3 expression, increasing the m6A modification of circ ‐ARL3; then, m6A reader YTHDC1 bound to m6A ‐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.
Source: IUBMB Life - Category: Research Authors: Tags: RESEARCH COMMUNICATION Source Type: research