MicroRNA-93 suppress colorectal cancer development via Wnt/β-catenin pathway downregulating

Tumour Biol. 2015 Mar;36(3):1701-10. doi: 10.1007/s13277-014-2771-6. Epub 2014 Nov 5.

Abstract

MicroRNA-93 (miR-93) is involved in several carcinoma progressions. It has been reported that miR-93 acts as a promoter or suppressor in different tumors. However, till now, the role of miR-93 in colon cancer is unclear. Herein, we have found that expression of miR-93 was lower in human colon cancer tissue and colorectal carcinoma cell lines compared with normal colon mucosa. Forced expression of miR-93 in colon cancer cells inhibits colon cancer invasion, migration, and proliferation. Furthermore, miR-93 may downregulate the Wnt/β-catenin pathway, which was confirmed by measuring the expression level of the β-catenin, axin, c-Myc, and cyclin-D1 in this pathway. Mothers against decapentaplegic homolog 7 (Smad7), as an essential molecular protein for nuclear accumulation of β-catenin in the canonical Wnt signaling pathway, is predicted as a putative target gene of miR-93 by the silico method and demonstrated that it may be suppressed by targeting its 3'UTR. These findings showed that miR-93 suppresses colorectal cancer development via downregulating Wnt/β-catenin, at least in part, by targeting Smad7. This study revealed that miR-93 is an important negative regulator in colon cancer and suggested that miR-93 may serve as a novel therapeutic agent that offers benefits for colon cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Colonic Neoplasms / genetics*
  • Cyclin D1 / genetics
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Signal Transduction
  • Wnt Proteins / genetics*
  • beta Catenin / genetics

Substances

  • 3' Untranslated Regions
  • MIRN93 microRNA, human
  • MicroRNAs
  • Wnt Proteins
  • beta Catenin
  • Cyclin D1