Dong K, Du Q, Cui X, Wan P, Kaltenmeier C, Luo J, Yan B, Yan Y, Geller DA. MicroRNA-301a (miR-301a) is induced in hepatocellular carcinoma (HCC) and down-regulates the expression of interferon regulatory factor-1. Biochem Biophys Res Commun. 2020 Jan 24;S0006-291X(20)30088-7. doi: 10.1016/j.bbrc.2020.01.034. PMID: 31987500.
Hepatocellular carcinoma (HCC) tumors evade death in part by downregulating expression of the tumor suppressor gene Interferon regulatory factor-1 (IRF-1). However, the molecular mechanisms accounting for IRF-1 suppression in HCC have not been well described. In this study, we identified a novel microRNA-301a (miR-301a) binding site in the 3′-untranslated region (3′- UTR) of the human IRF-1 gene and hypothesized a functional role for miR-301a in regulating HCC growth. We show that miR-301a is markedly upregulated in primary HCC tumors and HCC cell lines, while IRF-1 is down-regulated in a post-transcriptional manner. MiR-301a regulates basal and inducible IRF-1 expression in HCC cells with an inverse relationship between miR-301a and IRF-1 expression in HCC cells. Chronic hypoxia induces miR-301a in HCC in vitro and decreases IRF-1 expression. Finally, miR-301a inhibition increases apoptosis and decreases HCC cell proliferation. These findings suggest that targeting of IRF-1 by miR-301a contributes to the molecular basis for IRF-1 downregulation in HCC and provides new insight into the regulation of HCC by miRNAs.
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