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MicroRNA-301a (miR-301a) is induced in hepatocellular carcinoma (HCC) and down- regulates the expression of interferon regulatory factor-1

Kun DongDepartment of Pediatric Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, ChinaQiang DuDepartment of Surgery, University of Pittsburgh, Pittsburgh, PA, 15213, USAXiao CuiDepartment of Surgery, University of Pittsburgh, Pittsburgh, PA, 15213, USAPeiqi WanDepartment of Surgery, University of Pittsburgh, Pittsburgh, PA, 15213, USAChristof KaltenmeierDepartment of Surgery, University of Pittsburgh, Pittsburgh, PA, 15213, USAJing LuoDepartment of Surgery, University of Pittsburgh, Pittsburgh, PA, 15213, USABing YanDepartment of Surgery, University of Pittsburgh, Pittsburgh, PA, 15213, USAYihe YanDepartment of Surgery, University of Pittsburgh, Pittsburgh, PA, 15213, USADavid A. GellerDepartment of Surgery, University of Pittsburgh, Pittsburgh, PA, 15213, USA. Electronic address: [email protected]

2020en

ABI

Annotatsiya

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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Identifikatorlar

DOI: 10.1016/j.bbrc.2020.01.034

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