MicroRNA-1271 functions as a metastasis and epithelial-mesenchymal transition inhibitor in human HCC by targeting the PTP4A1/c-Src axis

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Abstract

MicroRNAs (miRNAs or miRs) have been shown to regulate hepatocellular carcinoma (HCC) metastasis. In the present study, we focused on the functions of miR-1271 in HCC metastasis. The downregulation of miR-1271 was found to be associated with to venous infiltration, an advanced TNM stage (III+IV stage) and a shorter survival time. Our in vitro and in vivo data demonstrated that miR-1271 prevented HCC cell migration and invasion, as well as the formation of lung metastatic clusters. In addition, miR-1271 was demonstrated to markedly inhibit the epithelial-mesenchymal transition (EMT) of HCC cells. Importantly, protein tyrosine phosphatase type IVA member 1 (PTP4A1) was identified as a direct downstream target of miR-1271 in HCC. Furthermore, we confirmed that the phosphorylation of c-Src at Tyr416 mediated by PTP4A1 was a potential anti-HCC mechanism of action of miR-1271. On the whole, our data indicate that miR-1271 inhibits HCC metastasis by targeting the PTP4A1/ c-Src signaling pathway and may serve as a prospective cancer therapeutic target for HCC.

Original languageEnglish
Pages (from-to)536-546
Number of pages11
JournalInternational Journal of Oncology
Volume52
Issue number2
DOIs
StatePublished - Feb 2018
Externally publishedYes

Keywords

  • Epithelial-mesenchymal transition
  • Hepatocellular carcinoma
  • Metastasis
  • MicroRNA-1271
  • Protein tyrosine phosphatase type IVA member 1

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