MiR-92a Promotes Cell Metastasis of Colorectal Cancer Through PTEN-Mediated PI3K/AKT Pathway

Ann Surg Oncol. 2015 Aug;22(8):2649-55. doi: 10.1245/s10434-014-4305-2. Epub 2014 Dec 17.

Abstract

Background: MicroRNAs regulate gene expression at the posttranscriptional level and play important roles in tumor development, progression, and metastasis. The aim of this study was to investigate the role of microRNA-92a (miR-92a) in metastasis of colorectal cancer (CRC).

Methods: One hundred fifty-eight CRC patients were enrolled. The expression of miR-92a, PTEN, and E-cadherin was analyzed by real-time PCR. Univariate (Kaplan-Meier) analysis was used to analyze primary outcomes included 5-year overall survival and tumor recurrence. CRC cell model studies were used to analyze the miR-92a-involved CRC metastasis.

Results: The expression of miR-92a in tumor tissues was significantly positively correlated with lymph node metastasis in CRC patients (p = 0.012). After adjusting for age, sex, and disease differentiation, this correlation remained significant (p = 0.01). In addition, there was a negative correlation between levels of miR-92a and the PTEN gene (p < 0.0001). No any association of miR-92a and E-cadherin was found (p = 0.128). Patients with high miR-92a/low PTEN had poorer overall survival and disease-free survival rates than those with high miR-92a/high PTEN, low miR-92a/high PTEN, and low miR-92a/low PTEN. The association of levels of miR-92a and PTEN with tumor cell migration in CRC was also confirmed in CRC cell models.

Conclusions: We suggest that miR-92a is involved in lymph node metastasis of CRC patients through PTEN-regulated PI3K/AKT signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cadherins / genetics*
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • Disease-Free Survival
  • Female
  • Gene Expression
  • Gene Knockdown Techniques
  • Humans
  • Lymphatic Metastasis
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • PTEN Phosphohydrolase / genetics*
  • PTEN Phosphohydrolase / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Survival Rate
  • Up-Regulation

Substances

  • Cadherins
  • MIRN92 microRNA, human
  • MicroRNAs
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human