MicroRNA-126 inhibits colon cancer cell proliferation and invasion by targeting the chemokine (C-X-C motif) receptor 4 and Ras homolog gene family, member A, signaling pathway

Oncotarget. 2016 Sep 13;7(37):60230-60244. doi: 10.18632/oncotarget.11176.

Abstract

MicroRNA-126 (miR-126) suppresses the migration, proliferation and invasion of colon cancer cells. However, the underlying mechanisms of miR-126 in colon cancer have not been fully elucidated. In this study, in vivo experiments revealed that miR-126 inhibits colon cancer growth and metastasis. Furthermore, miR-126 was down-regulated in human colon cancer tissue, and its expression was inversely correlated with TNM stage and metastasis of patients. Low level of miR-126 identified patients with poor prognosis. And we found that miR-126 expression was negatively correlated with the expression levels of chemokine (C-X-C motif) receptor 4 (CXCR4) and components of signaling pathway of Ras homolog gene family, member A (RhoA) in vitro and in vivo. Moreover, we verified that miR-126 negatively regulated CXCR4 and RhoA signaling in vitro. In addition, either in miR-126-overexpressing or in miR- 126-silenced colon cancer cells, the restoration of CXCR4 could significantly reverse the proliferation and invasion, as well as abolish the effects of miR-126 on RhoA signaling pathway. Collectively, these results demonstrated that miR-126 acts as a tumor suppressor by inactivating RhoA signaling via CXCR4 in colon cancer. And miR-126 may serve as a prognostic marker for monitoring and treating colon cancer.

Keywords: CXCR4; RhoA; colon cancer; microRNA-126 (mir-126).

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • HCT116 Cells
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Middle Aged
  • Models, Genetic
  • Neoplasm Invasiveness
  • RNA Interference
  • Receptors, CXCR4 / genetics*
  • Receptors, CXCR4 / metabolism
  • Signal Transduction / genetics
  • rhoA GTP-Binding Protein / genetics*
  • rhoA GTP-Binding Protein / metabolism

Substances

  • CXCR4 protein, human
  • MIRN126 microRNA, human
  • MicroRNAs
  • Receptors, CXCR4
  • rhoA GTP-Binding Protein