Role of miR-541-3p/TMPRSS4 in the metastasis and EMT of hepatocellular carcinoma

Y.-H. Xia, L. Ren, J.-Z. Li, F. Gao

Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China. gaofei_19790813@163.com

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• Oncology

OBJECTIVE: The aim of this study was to investigate the role of miR-541-3p in hepatocellular carcinoma (HCC), and to explore the possible underlying mechanism.

PATIENTS AND METHODS: 80 pairs of cancerous and para-cancerous tissues were collected in this study. Human HCC SMMC-7721 cells and normal liver HL-7702 cells were enrolled as well. Quantitative Polymerase Chain Reaction (qPCR) was performed to detect the expression level of miR-541-3p in tissues and cells. Potential target genes of miR-541-3p were screened and confirmed by online prediction websites and Dual-Luciferase reporter gene assay, respectively. SMMC-7721 cells were used for functional experiments in vitro. Cell proliferation was detected by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. The invasion and migration of the cells were evaluated by transwell and scratch wound-healing assay, respectively. Furthermore, the epithelial-mesenchymal transition (EMT) associated markers were measured by Western blot assay.

RESULTS: MiR-541-3p was lowly expressed in both HCC tissues and cells. Transmembrane protease serines 4 (TMPRSS4) was defined as a functional target of miR-541-3p. The miR-541-3p/TMPRSS4 axis showed containment in HCC cells, such as proliferation, invasion and migration. These effects might be manifested by altering the expressions of EMT-related molecular proteins, including TGF-β, E-cadherin and N-cadherin.

CONCLUSIONS: Our data indicated that miR-541-3p suppressed the invasion and migration of HCC cells by directly targeting and inhibiting TMPRSS4 protein expression. Furthermore, the newly identified miR-541-3p/TMPRSS4 axis provided new insight into the pathogenesis of HCC. It might also serve as a novel potential therapeutic target for HCC treatment.

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