Hepatocyte‐Enriched miRNA‐193b‐3p Promotes Hepatitis B Virus Replication by Dual Activation of Viral Core Promoter Activity and Autophagy Induction by Targeting IGF‐1R

ABSTRACT Hepatitis B virus (HBV) infection is a principal cause of severe liver disease in humans and is associated with increased levels of specific serum or intracellular microRNAs (miRNAs). Among these, miR‐193b‐3p is a liver‐enriched miRNA; however, its role in HBV replication remains unknown. This study aimed to investigate the influence of chronic HBV infection on miR‐193b‐3p levels in the peripheral blood and liver tissues of patients with chronic hepatitis B (CHB), evaluate the effect of miR‐193b‐3p on HBV replication both in vitro and in vivo, and elucidate the potential underlying mechanisms. We showed that hepatic miR‐193b‐3p levels in patients with CHB were significantly elevated compared with those in healthy controls. Ectopic expression of miR‐193b‐3p significantly enhanced HBV replication and transcription in different hepatoma cell lines. Furthermore, we identified IGF‐1R as a direct target through which miR‐193b‐3p regulates HBV replication. Mechanistically, miR‐193b‐3p increased HBV core promoter activity via the IGF‐1R/FXRα axis, thereby enhancing HBV transcription. Additionally, miR‐193b‐3p increased IGF‐1R/Akt/MDM2/p53 signaling‐mediated autophagy induction, which in turn facilitated increased HBV post‐transcriptional activity. Collectively, hepatocyte‐enriched miR‐193b‐3p exerts a proviral effect on HBV replication through dual synergistic mechanisms, offering novel insights into its role in HBV replication and potential therapeutic implications in CHB infection.