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ORIGINAL RESEARCH article

Front. Cell. Infect. Microbiol.
Sec. Molecular Viral Pathogenesis
Volume 14 - 2024 | doi: 10.3389/fcimb.2024.1421195
This article is part of the Research Topic Impacts of virus infection on cellular stress, cytoskeleton dynamics and induction of antiviral states View all 3 articles

IFN-treated macrophage-derived exosomes prevents HBV-HCC migration and invasion via regulating miR-106b-3p/PCGF3/PI3K/AKT signaling axis

Provisionally accepted
Jing Chen Jing Chen Qi Yin Qi Yin hen s. Xu hen s. Xu qing x. Tan qing x. Tan Yu Liang Yu Liang hui c. Chen hui c. Chen Li Li Li Li Tao Shen Tao Shen *
  • The First People’s Hospital of Yunnan Province, Kunming, China

The final, formatted version of the article will be published soon.

    Studies revealed that exosomes from IFN-α-treated liver non-parenchymal cells (IFN-exo) mediate antiviral activity. MiR-106b-3p has been shown to play a paradoxical role in disease progressing from different studies. However, its specific role in HBV-related hepatocellular carcinoma (HBV-HCC) and the underlying mechanism remains unclear.Huh7 cells transient transfected with plasmids of HBV-C2 and B3 were co-cultured with IFN-exo. Cell supernatants were collected to detect miR-106b-3p, HBsAg, HBeAg and HBV DNA levels. Cell proliferation, apoptosis, migration and invasion were analyzed. The putative targets of miR-106b-3p were identified by a dual-luciferase reporter system. The expression of PCGF3, migratory proteins (MMP2/9), and the PI3K/AKT signaling pathway-related proteins were assessed by western blot. The expression of PCGF3 mRNA was quantitative analyzed by using 52 pairs of paraffin-embedded tissues from HCC patients'. siRNAs-PCGF3 were used to knocked-down PCGF3 expression.The expression of miR-106b-3p was significantly higher in THP-1 cells and supernatants treated with IFN-exo than those untreated. Significantly increased expression of miR-106b-3p and decreased expression of HBsAg and HBV DNA were observed in Huh7-C2/B3 cells treated with IFN-exo. In addition, miR-106b-3p was directly target to PCGF3. Scratch healing assay and transwell assay showed that either IFN-exo or miRNA-106-3p over-expression, or siRNAs-PCGF3 inhibited migration and invasion of Huh7-C2/B3 cells, and subsequently resulted in suppression of p-AKT/AKT and p-PI3K/PI3K. Notably, the expression level of PCGF3 was significantly lower in HBeAg (+)-HCC tumor tissues than HBeAg (-)-HCC tumor.IFN-α-induced macrophage-derived miR-106b-3p inhibits HBV replication, HBV-Huh7 cells migration and invasion via regulating PCGF3/PI3K/AKT signaling axis. miR-106b-3p and PCGF3 were potential biomarkers in the prevention and treatment of HBV-HCC.

    Keywords: IFN-α-induced macrophage-derived exosome, miR-106b-3p, PCGF3, HBV-related hepatocellular carcinoma, PI3K/Akt pathway

    Received: 22 Apr 2024; Accepted: 05 Sep 2024.

    Copyright: © 2024 Chen, Yin, Xu, Tan, Liang, Chen, Li and Shen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Tao Shen, The First People’s Hospital of Yunnan Province, Kunming, China

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