Deregulated expression of miR-145 in manifold human cancer cells

Exp Mol Pathol. 2013 Aug;95(1):91-7. doi: 10.1016/j.yexmp.2013.05.003. Epub 2013 May 25.

Abstract

MicroRNAs play important roles in the processes of tumor initiation and progression. The expression level of miR-145 in gastric, liver, and cervical cancers has been rarely investigated. Whether miR-145 may function as a common tumor suppressor in the generation of tumor phenotype needs to be clarified. miR-145 expression was determined by RT-qPCR in various human cancer tissues including those of gastric, liver, colon, and cervical cancers. Cancer cell lines were transfected with miR-145 precursor, anti-miR-145 inhibitor, or negative control, and cells' proliferation, migration, and invasion activities were analyzed. The gene target of miR-145 was confirmed by luciferase assay and Western blot. The miR-145 expression level was lower by 37.68-, 2.64-, 2.69- and 2.39-fold in gastric, liver, colon, and cervical cancer tissues, respectively, compared to corresponding nontumorous controls. Moreover, miR-145 levels were significantly downregulated in various cancer cell lines. We further demonstrated that miR-145 could suppress anchorage-independent growth and cell motility in both the liver cancer cell line Hep-G2 and the gastric cancer cell line MKN-45, and inhibited cell proliferation in a cell type-specific manner. Insulin receptor substrate-1 (IRS1) was identified as a target gene of miR-145, by which miR-145 was able to suppress cell proliferation. miR-145 suppresses cell proliferation, anchorage-independent growth, cell motility, and may serve as a tumor suppressor.

Keywords: Cell motility; Cell proliferation; Tumor; miR-145.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Colonic Neoplasms / genetics
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, Tumor Suppressor
  • Humans
  • Insulin Receptor Substrate Proteins / genetics
  • Insulin Receptor Substrate Proteins / metabolism
  • Liver Neoplasms / genetics
  • MicroRNAs / genetics*
  • Reference Values
  • Stomach Neoplasms / genetics
  • Tumor Stem Cell Assay
  • Uterine Cervical Neoplasms / genetics

Substances

  • IRS1 protein, human
  • Insulin Receptor Substrate Proteins
  • MIRN145 microRNA, human
  • MicroRNAs