MicroRNA-96-5p Induces the Epithelial-mesenchymal Transition to Promote the Metastasis of Hepatocellular Carcinoma by Post-transcriptionally Downregulating Talin 1
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Numerous microRNAs (miRNAs) have been shown to play an important regulatory role in the progression of hepatocellular carcinoma (HCC). miR-96-5p, a cancer-related microRNA, was previously reported to inhibit cell apoptosis in HCC, but the function and underlying mechanism of miR-96-5p's involvement in HCC metastasis and progression still remain unknown. In this study, we showed that a significant up-regulation of miR-96-5p in HCC tissues and cell lines, and its increased expression, are associated with microvascular invasion and with the TNM stages of HCC patients. Gain-of-function assays revealed that miR-96-5p induced the epithelial-mesenchymal transition (EMT) to promote the migration and invasion of HCC in vitro. The expression of TLN1 (Talin 1) is significantly decreased in HCC tissues and is inversely correlated to miR-96-5p levels. Notably, through a luciferase reporter assay and a Western blot analysis, TLN1 was confirmed to be a direct target gene of miR-96-5p. Furthermore, results of cell functional assays revealed that the over-expression of TLN1 partially reverses the promotive effects of miR-96-5p overexpression on the migration, invasion, and EMT of HCC. Overall, data from the present study demonstrate that miR-96-5p induces EMT to promote the migration and invasion of HCC by post-transcriptionally downregulating TLN1, indicating that the miR-96-5p/TLN1 axis might provide a potential therapeutic target for the treatment of HCC.
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