miRNA-185 serves as a prognostic factor and suppresses migration and invasion through Wnt1 in colon cancer

Eur J Pharmacol. 2018 Apr 15:825:75-84. doi: 10.1016/j.ejphar.2018.02.019. Epub 2018 Feb 15.

Abstract

Colon cancer is one of the deadliest cancers worldwide; abnormal microRNA expression is common during colon cancer development. The aim of the present study was to elucidate the role played by miR-185 in this context. We used quantitative real-time PCR (qRT-PCR) to measure miR-185 expression levels in colon cancer cell lines. The effects of miR-185 on colon cancer cell proliferation and invasion were assessed using the MTT, colony-forming, wound-healing, and transwell assays. A luciferase activity assay was used to confirm the target of miR-185. Our data showed that miR-185 was significantly down-regulated in colon cancer cells and colonic cancer tissues compared with NCM460 normal colonic epithelial cells and adjacent normal tissues. A functional analysis revealed that ectopic expression of miR-185 significantly inhibited colon cancer cell proliferation, colony formation, migration, and invasion. In addition, western blot, qRT-PCR, and luciferase assays confirmed in colon cancer cells that Wnt1 was a downstream target of miR-185, in turn suppressing β-catenin-mediated signaling. In conclusion, we found that miR-185 inhibits colon cancer cell proliferation and invasion by targeting Wnt1, and that it serves as a tumor suppressor, indicating that the modulation of miR-185 levels may potentially be therapeutic in colon cancer patients.

Keywords: Colon cancer; MiRNA-185; Wnt1; β-catenin signaling pathway.

MeSH terms

  • Cell Movement / genetics*
  • Cell Proliferation / genetics
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology*
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • HCT116 Cells
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Prognosis
  • Signal Transduction / genetics
  • Wnt1 Protein / genetics*

Substances

  • MicroRNAs
  • WNT1 protein, human
  • Wnt1 Protein