Epigenetic silencing of miR-137 contributes to early colorectal carcinogenesis by impaired Aurora-A inhibition

Oncotarget. 2016 Nov 22;7(47):76852-76866. doi: 10.18632/oncotarget.12719.

Abstract

MicorRNA-137 is silenced in human colorectal cancer tissues and colon polyps. Our study showed that the decreased expression of miR-137 is significantly different in various types of polyp which maintain different potentials to lead to CRC development. The expression of miR-137 gradually decreases during the process of colorectal carcinogenesis. Receiver operating characteristic curve (ROC) analysis indicates that the loss of miR-137 expression in colon polyps can serve as a biomarker to predict the predisposition of colorectal carcinogenesis. By cell model and xenograft animal model, the enforced expression of miR-137 in colorectal cancer cells can inhibit cell proliferation and tumor formation, induce G2/M arrest, and lead to apoptosis. The expression pattern of miR-137 and Aurora-A or PTGS2 is negatively correlated in human colorectal cancer tissues and colon polyps. Those effects induced by overexpressed miR-137 can be rescued by the overexpression of Aurora-A. In summary, our study suggests that the loss of miR-137 expression in colon polyps can serve as a biomarker to predict the tendency toward to CRC formation through the impaired inhibitory effect of Aurora-A. The investigation of the regulatory mechanism of miR-137-mediated Aurora-A inhibition may shed new light on the early prognosis of cancer therapy for CRC in the future.

Keywords: Aurora-A; COX2; colorectal cancer; epigenetic regulation; miR-137.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Aurora Kinase A / genetics*
  • Cell Line, Tumor
  • Cell Proliferation
  • Colonic Polyps / genetics*
  • Colorectal Neoplasms / genetics*
  • Cyclooxygenase 2 / genetics*
  • DNA Methylation*
  • Down-Regulation
  • Epigenesis, Genetic
  • Female
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Humans
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Transplantation

Substances

  • MIRN137 microRNA, human
  • MicroRNAs
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • AURKA protein, human
  • Aurora Kinase A