miR-130a-5p/TFPI2 axis promotes invasion of hepatocellular carcinoma by altering epithelial-to-mesenchymal transition.

BACKGROUND: MicroRNAs (miRNAs), particularly miR-130a-5p, play pivotal roles in the tumorigenesis and progression of hepatocellular carcinoma (HCC) by participating in diverse biological processes. The objective of this study was to elucidate the mechanistic basis by which miR-130a-5p regulates the expression of tissue factor pathway inhibitor-2 (TFPI2) and to demonstrate the subsequent impact of the miR-130a-5p/TFPI2 axis on HCC invasion. METHODS: Expression levels of miR-130a-5p and TFPI2 were quantified in HepG2 cell lines using quantitative real-time PCR (qRT-PCR). Western blot and qRT-PCR were employed to assess the expression of TFPI2 and epithelial-to-mesenchymal transition (EMT)-related proteins in both cancer cells and tissues. miR-130a-5p knockdown and TFPI2 overexpression were achieved through transfection of HepG2 cells with short hairpin RNA (shRNA) and synthetic overexpression plasmids, respectively. A dual luciferase reporter assay was conducted to verify the binding of miR-130a-5p to TFPI2. Migration and invasion capabilities of cancer cells were evaluated using Transwell migration and invasion assays. A mouse xenograft tumor model was established to investigate tumor growth in vivo. Immunohistochemical (IHC) staining was utilized to examine the expression of EMT-related proteins in tumor tissues. RESULTS: The dual-luciferase reporter assay confirmed that miR-130a-5p binds to the 3' untranslated region (3'UTR) of TFPI2 mRNA, inhibiting its luciferase activity. Western blot analysis revealed that miR-130a-5p negatively regulates TFPI2 protein expression and promotes EMT molecular events by targeting TFPI2 in HCC cells. Transwell assays demonstrated that downregulation of miR-130a-5p and upregulation of TFPI2 inhibited the migration and invasion abilities of HCC cells in vitro. Silencing of miR-130a-5p was found to retard the growth of HCC xenografts in vivo, decrease TFPI2 expression, and alter the EMT process. CONCLUSIONS: miR-130a-5p binds to TFPI2 mRNA and promotes HCC cell migration, invasion, and xenograft tumor growth by regulating the EMT process. These findings suggest that the miR-130a-5p/TFPI2 axis may represent a promising therapeutic target for the treatment of HCC.