Jing Chen, Qi Yin, Shiheng Xu, Xiaoqing Tan, Yu Liang, Chaohui Chen, Li Li, Tao Zhang, Tao Shen
{"title":"经 IFN 处理的巨噬细胞衍生外泌体可通过调节 miR-106b-3p/PCGF3/PI3K/AKT 信号轴阻止 HBV-HCC 迁移和侵袭。","authors":"Jing Chen, Qi Yin, Shiheng Xu, Xiaoqing Tan, Yu Liang, Chaohui Chen, Li Li, Tao Zhang, Tao Shen","doi":"10.3389/fcimb.2024.1421195","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Method: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1421195"},"PeriodicalIF":4.6000,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551115/pdf/","citationCount":"0","resultStr":"{\"title\":\"IFN-treated macrophage-derived exosomes prevents HBV-HCC migration and invasion via regulating miR-106b-3p/PCGF3/PI3K/AKT signaling axis.\",\"authors\":\"Jing Chen, Qi Yin, Shiheng Xu, Xiaoqing Tan, Yu Liang, Chaohui Chen, Li Li, Tao Zhang, Tao Shen\",\"doi\":\"10.3389/fcimb.2024.1421195\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Method: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":12458,\"journal\":{\"name\":\"Frontiers in Cellular and Infection Microbiology\",\"volume\":\"14 \",\"pages\":\"1421195\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-10-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551115/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Cellular and Infection Microbiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fcimb.2024.1421195\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Cellular and Infection Microbiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fcimb.2024.1421195","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
IFN-treated macrophage-derived exosomes prevents HBV-HCC migration and invasion via regulating miR-106b-3p/PCGF3/PI3K/AKT signaling axis.
Background: 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.
Method: 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.
Results: 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.
Conclusion: 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.
期刊介绍：
Frontiers in Cellular and Infection Microbiology is a leading specialty journal, publishing rigorously peer-reviewed research across all pathogenic microorganisms and their interaction with their hosts. Chief Editor Yousef Abu Kwaik, University of Louisville is supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
Frontiers in Cellular and Infection Microbiology includes research on bacteria, fungi, parasites, viruses, endosymbionts, prions and all microbial pathogens as well as the microbiota and its effect on health and disease in various hosts. The research approaches include molecular microbiology, cellular microbiology, gene regulation, proteomics, signal transduction, pathogenic evolution, genomics, structural biology, and virulence factors as well as model hosts. Areas of research to counteract infectious agents by the host include the host innate and adaptive immune responses as well as metabolic restrictions to various pathogenic microorganisms, vaccine design and development against various pathogenic microorganisms, and the mechanisms of antibiotic resistance and its countermeasures.
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