MicroRNA-92a functions as an oncogene in colorectal cancer by targeting PTEN

Dig Dis Sci. 2014 Jan;59(1):98-107. doi: 10.1007/s10620-013-2858-8. Epub 2013 Sep 12.

Abstract

Background: Our previous studies show that microRNA-92a (miR-92a) is overexpressed in colorectal cancer (CRC) and is thought to be correlated with the development of the cancer. However, its biological role in CRC remains poorly understood.

Aims: The aim of the study was to determine the role of miR-92a and to elucidate its regulatory mechanism in CRC.

Methods: The expression levels of miR-92a and phosphatase and tensin homologue (PTEN) were detected by qRT-PCR and western blot. MTT, migration and invasion assays were used to examine the proliferation, migration and invasion of pre-miR-92a transfected SW480 cells, and a mouse model was used to investigate tumorigenesis. In addition, the regulation of PTEN by miR-92a was evaluated by qRT-PCR, western blot and luciferase reporter assays.

Results: The expression of miR-92a was significantly up-regulated in the tissues of CRC patients with lymph node metastasis. The ectopic expression of miR-92a enhanced CRC cell proliferation, migration and invasion. Similar results were found in xenograft assay performed in nude mice. Up-regulation of miR-92a induced EMT in CRC cells. There was an inverse correlation between the levels of miR-92a and PTEN in CRC tissues. The overexpression of miR-92a in CRC cells decreased PTEN expression at the translational level, and decreased PTEN-driven luciferase-reporter activity.

Conclusions: Our results demonstrated that miR-92a induced EMT and regulated cell growth, migration and invasion in the SW480 cells, at least partially, via suppression of PTEN expression. MiR-92a may serve as a novel therapeutic target in colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma / etiology
  • Carcinoma / metabolism*
  • Cell Movement / genetics
  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • Colorectal Neoplasms / etiology
  • Colorectal Neoplasms / metabolism*
  • Epithelial-Mesenchymal Transition
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Oncogenes*
  • PTEN Phosphohydrolase / antagonists & inhibitors*
  • PTEN Phosphohydrolase / metabolism*
  • Translational Research, Biomedical

Substances

  • MIRN92 microRNA, human
  • MicroRNAs
  • PTEN Phosphohydrolase
  • PTEN protein, human