Role of microRNA 30a targeting insulin receptor substrate 2 in colorectal tumorigenesis

Mol Cell Biol. 2015 Mar;35(6):988-1000. doi: 10.1128/MCB.01242-14. Epub 2015 Jan 12.

Abstract

MicroRNAs (miRNAs) are dysregulated in many types of malignant diseases, including colorectal cancer. miRNA 30a (miR-30a) is a member of the miR-30 family and has been implicated in many types of cancers. In this study, we determined the expression of miR-30a in human colon cancer tissues and cell lines. miR-30a was found to be significantly downregulated in both the tissues and cell lines. Furthermore, overexpression of miR-30a inhibited, while silencing of miR-30a promoted, cell proliferation, migration, and invasion in vitro. Consistently, stable overexpression of miR-30a suppressed the growth of colon cancer cell xenografts in vivo. Moreover, bioinformatic algorithms and luciferase reporter assays revealed that insulin receptor substrate 2 (IRS2) is a direct target of miR-30a. Further functional studies suggested that repression of IRS2 by miR-30a partially mediated the tumor suppressor effect of miR-30a. In addition, miR-30a inhibited constitutive phosphorylation of Akt by targeting IRS2. Additionally, clinicopathological analysis indicated that miR-30a has an inverse correlation with the staging in patients with colon cancer. Taken together, our study provides the first evidence that miR-30a suppressed colon cancer cell growth through inhibition of IRS2. Thus, miR-30a might serve as a promising therapeutic strategy for colon cancer treatment.

Publication types

  • Retracted Publication

MeSH terms

  • Animals
  • Carcinogenesis / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cell Transformation, Neoplastic / genetics
  • Colorectal Neoplasms / genetics*
  • Down-Regulation / genetics
  • Female
  • Genes, Tumor Suppressor
  • HCT116 Cells
  • Humans
  • Insulin Receptor Substrate Proteins / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Proto-Oncogene Proteins c-akt / genetics

Substances

  • IRS2 protein, human
  • Insulin Receptor Substrate Proteins
  • MicroRNAs
  • Proto-Oncogene Proteins c-akt