miR-26a-5p suppresses tumor metastasis by regulating EMT and is associated with prognosis in HCC

Clin Transl Oncol. 2017 Jun;19(6):695-703. doi: 10.1007/s12094-016-1582-1. Epub 2016 Nov 18.

Abstract

Objective: To determine the role of miR-26a-5p in tumor invasion and metastasis in hepatocellular carcinoma (HCC).

Methods: We evaluated miR-26a-5p expression in HCC tissues by quantitative PCR and then analyzed its clinical significance using a Cox regression model. Transwell and nude mouse models were used to examine tumor metastasis in vitro and in vivo, respectively. The relationship between miR-26a-5p and epithelial-mesenchymal transition was also investigated by q-PCR and western blot.

Results: Strong downregulation of miR-26a-5p was observed in tumor tissues compared to paired adjacent normal tissues. Moreover, patients with low miR-26a-5p expression had a significantly poorer prognosis than those with high expression. The multivariate analysis indicated that miR-26a-5p expression was an independent prognostic indicator. The experimental transwell model and athymic mouse model revealed that miR-26a-5p depressed tumor metastasis in vitro and in vivo, respectively. In addition, the decreased miR-26a-5p level observed in HCC was associated with reduced E-cadherin expression and upregulation of vimentin, which affects the molecular mechanism of EMT.

Conclusion: Downregulation of miR-26a-5p promotes tumor metastasis by targeting EMT and influences the prognosis of HCC patients. Therefore, miR-26a-5p has potential as a new biomarker and therapeutic target.

Keywords: EMT; Prognosis; Tumor metastasis; miR-26a-5p.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology*
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Heterografts
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / genetics
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology*
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Prognosis

Substances

  • MIRN26A microRNA, human
  • MicroRNAs