MicroRNA-128 suppresses cell growth and metastasis in colorectal carcinoma by targeting IRS1

Oncol Rep. 2015 Nov;34(5):2797-805. doi: 10.3892/or.2015.4251. Epub 2015 Sep 8.


Evidence has shown that microRNAs play important roles in tumor development, progression, and metastasis. miR-128 has been reported to be deregulated in different tumor types, whereas the function of miR-128 in colorectal carcinoma (CRC) largely remains to be elucidated. The aim of the present study was to investigate the clinical significance, biological effects and underlying mechanisms of miR-128 in CRC using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. It was found that the expression of miR-128 was downregulated in CRC tissues and cell lines as determined by RT-qPCR. Furthermore, the expression of miR-128 in tumor tissues was significantly negatively correlated with TNM stage and lymph node metastasis in CRC patients. Functional assay revealed that the overexpression of miR-128 inhibited CRC cell proliferation, colony formation, migration and invasion and promoted apoptosis in vitro, and suppressed CRC xenograft tumor growth in vivo. In addition, insulin receptor substrate 1 (IRS1), a key mediator in oncogenic insulin-like growth factor (IGF) signaling, was confirmed as a direct target of miR-128 by a luciferase reporter assay. Western blot analysis indicated that the overexpression of miR-128 significantly downregulated IRS1 expression and its downstream Akt signaling in CRC cells. Moreover, miR-128 was negatively associated with IRS1 in CRC tissues compared to adjacent non-tumor tissues. Taken together, these data suggested that miR-128 serves as a tumor suppressor and blocks CRC growth and metastasis by targeting IRS1.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Humans
  • Insulin Receptor Substrate Proteins / genetics*
  • Male
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neoplasm Transplantation


  • IRS1 protein, human
  • Insulin Receptor Substrate Proteins
  • MIRN128 microRNA, human
  • MicroRNAs