Background: Circular RNAs (circRNAs) play an important regulatory role in various cancers, including hepatocellular carcinoma (HCC). This study aimed to investigate the function of hsa_circ_0006942 (circ-ATP5H) in hepatitis B virus (HBV)-associated HCC and its underlying mechanism.
Methods: The levels of circ-ATP5H, miR-138-5p and tumor necrosis factor alpha-induced protein 3 (TNFAIP3 ) were determined using quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot assay. The copies of HBV DNA were examined using qRT-PCR. The levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were detected via enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter assay was used to analyze the interactions among circ-ATP5H, miR-138-5p and TNFAIP3 .
Results: Circ-ATP5H and TNFAIP3  levels were increased, while miR-138-5p level was reduced in HBV-positive HCC tissues and cells. Knockdown of circ-ATP5H hindered HBV DNA replication and decreased HBsAg and HBeAg levels in HBV-infected cells. Circ-ATP5H silencing suppressed HBV replication and expression by regulating miR-138-5p. Moreover, miR-138-5p blocked HBV replication and expression via targeting TNFAIP3 . Furthermore, circ-ATP5H up-regulated TNFAIP3  via absorbing miR-138-5p.
Conclusion: Circ-ATP5H promoted HBV replication and expression through modulating miR-138-5p/TNFAIP3  axis, suggesting a new biomarker for HBV-related HCC treatment.
Keywords: hepatitis B virus, hepatocellular carcinoma, circ-ATP5H, miR-138-5p, TNFAIP3