MiR-650 represses high-risk non-metastatic colorectal cancer progression via inhibition of AKT2/GSK3β/E-cadherin pathway

Oncotarget. 2017 Jul 25;8(30):49534-49547. doi: 10.18632/oncotarget.17743.

Abstract

Although 5-year survival rate of non-metastatic colorectal cancer (CRC) is high, about 10% of patients in stage I and II still develop into metastatic CRC and eventually die after resection. Currently, there is no effective biomarker for predicting the prognosis of non-metastatic CRC in clinical practice. In this study, we identified miR-650 as a biomarker for prognosis prediction. We observed that the expression of miR-650 in tumor tissues had a positive association with overall survival. MiR-650 inhibited cell growth and invasion in vitro and in vivo. Furthermore, miR-650 targeted AKT2 and repressed the activation of the AKT pathway (AKT2/GSK3β/E-cadherin). Thus it induced the translocation of E-cadherin and β-catenin in cancer cells. Our results highlight the potential of miR-650 as a prognostic prediction biomarker and therapeutic target in non-metastatic CRC via inhibition of the AKT2/GSK3β/E-cadherin pathway.

Keywords: AKT pathway; microRNA; non-metastatic colorectal cancer; prognosis biomarker.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cadherins / metabolism*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glycogen Synthase Kinase 3 beta / metabolism*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Models, Biological
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA Interference
  • Signal Transduction*

Substances

  • Cadherins
  • MIRN650 microRNA, human
  • MicroRNAs
  • AKT2 protein, human
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt