MiR-22 regulated T cell differentiation and hepatocellular carcinoma growth by directly targeting Jarid2

xlomafota13 shared this article with you from Inoreader MiR-22 regulated T cell differentiation and hepatocellular carcinoma growth by directly targeting Jarid2 Via American Journal of Cancer Research Am J Cancer Res. 2021 May 15;11(5):2159-2173. eCollection 2021. ABSTRACT MiR-22 has been demonstrated to inhibits tumor growth in several cancers. However, its function in the tumor microenvironment is still unclear, especially for T cell differentiation. Here, miR-22 expression in the circulating T cells from hepatocellular carcinoma (HCC) patients and healthy controls was analyzed with quantitative polymerase chain reaction (qPCR). Diethylnitrosamine (DEN)/phenobarbital (PB)-mediated primary HCC and Hepa1-6 subcutaneous tumor mouse models were established and subjected to lenti-miR-22 injection. Mice immunoreconstituted with miR-22-overexpressing T cells were employed to investigate the antitumor effect of miR-22 in mice. Luciferase assay, immunofluorescent staining, in vitro Th17 cell differentiation assay, and rescue experiments were employed to investigate the mechanism underlying the miR-22-mediated regulation of Th17 cell differ entiation and liver tumor growth. Results confirmed the dramatic downregulation of miR-22 expression in malignant tissues and circulating T cells from patients with HCC. MiR-22 expression correlated with good prognosis of patients. Overexpression of miR-22 impaired the DEN/PB-induced primary HCC formation and the growth of Hepa1-6 subcutaneous tumors by promoting Th17 differentiation. Injection of miR-22-overexpressing T cells in irradiated mice resulted in the inhibition of Hepa1-6 subcutaneous tumor growth via Th17 differentiation promotion. MiR-22 could directly bind to Jarid2, which played an important role during the miR-22-mediated regulation of Th17 differentiation. Taken together, our study expands the understanding of miR-22 function and provides a therapy target for HCC. PMID:34094675 | PMC:PMC8167680 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.