Cell Death and Disease · 2018 · 101 citations · 23 references
MedicineCancer BiologyOncologyMolecular OncologySignal TransductionTumor ProgressionCancer Cell SignalingCancer ProgressionHepatocellular CarcinomaLiver CancerMicrorna BiologyMicrorna-mediated RegulationHepatocellular Carcinoma PathogenesisLuciferase Reporter AssaysLuciferase ReportersMicrorna In CancerMicrorna Regulation In CancerReceptor Protein Tyrosine PhosphatasesReceptor Tyrosine Kinase CascadesTumor Cell Proliferation
Growing evidence suggests that aberrant microRNA (miRNA) expression contributes to hepatocellular carcinoma (HCC) development and progression. However, the potential role and mechanism of miR-665 in the progression of liver cancer remains largely unknown. Our current study showed that miR-665 expression was upregulated in HCC cells and tissues. High expression of miR-665 exhibited more severe tumor size, vascular invasion and Edmondson grading in HCC patients. Gain- or loss-of-function assays demonstrated that miR-665 promoted cell proliferation, migration, invasion, and the epithelial-mesenchymal transition (EMT) of HCC cells in vitro and in vivo. Tyrosine phosphatase receptor type B (PTPRB) was downregulated in HCC tissues, and was negatively correlated with miR-665 expression. Through western blotting and luciferase reporter assay, PTPRB was identified as a direct downstream target of miR-665. Restoration of PTPRB reverses the effects of miR-665 on HCC migration, invasion, and cell proliferation. A mechanistic study showed that PTPTRB mediated the functional role of miR-665 through regulation of the Hippo signaling pathway. In conclusion, our results suggested that miR-665 was a negative regulator of the PTPRB and could promote tumor proliferation and metastasis in HCC through decreasing Hippo signaling pathway activity, which can be a potential target for HCC treatment.
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