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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.

Yingying Deng·Jiaxin Zheng·Fahong Li·Hecun Zou·Shijun Tian·Zhenyu Zhao·Huaqing Zeng·Yongzhen Zhai·Wanyu Deng·Jiming Zhang·Mengji Lu·Bei Jia·Yong Lin
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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.

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HumansMicroRNAsVirus ReplicationAutophagyHepatitis B virusHepatocytesReceptor, IGF Type 1Hepatitis B, ChronicPromoter Regions, GeneticMaleFemaleAnimalsAdultMiddle AgedLiverFXRαIGF‐1Rautophagyhepatitis B virusmiR‐193b‐3pJournal ArticleResearch Support, Non-U.S. Gov't

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Yingying Deng, Jiaxin Zheng, Fahong Li, Hecun Zou, Shijun Tian, Zhenyu Zhao, Huaqing Zeng, Yongzhen Zhai, Wanyu Deng, Jiming Zhang, Mengji Lu, Bei Jia, Yong Lin. 2025. 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.. https://doi.org/10.1002/jmv.70330

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