MicroRNA-126 inhibits tumor cell growth and its expression level correlates with poor survival in non-small cell lung cancer patients

PLoS One. 2012;7(8):e42978. doi: 10.1371/journal.pone.0042978. Epub 2012 Aug 10.

Abstract

Background: It is controversial whether microRNA-126 is a tumor suppressive or oncogenic miRNA. More experiments are needed to determine whether microRNA-126 is associated with non-small cell lung cancer risk and prognosis.

Methods: Over-expression of microRNA-126 was performed to evaluate the cell invasion and tumor growth in non-small cell lung cancer (NSCLC) cell lines and nude mouse xenograft model. Gain-of-function experiments and luciferase assays were performed to reveal the relationship between microRNA-126 and PI3K-Akt signal pathway in A549 cells. We analyzed the associations of the microRNA-126 expression between genetic variants within microRNA-126 and clinical information including smoking status, sex, age, and histological type and the tumor stage.

Results: Over-expression of microRNA-126 in NSCLC cell lines decreased cell proliferation in vitro and tumor growth in the nude mouse xenograft model. And microRNA-126 repressed the activity of PI3K-Akt pathway by targeting binding sites in the 3'-untranslated region of PI3KR2 mRNA. The expression level of microRNA-126 was decreased in NSCLC lines and tumor tissues. The patients with low microRNA-126 expression had significantly poorer survival time than those with high microRNA-126 expression (means for survival time (month): 24.392±1.055 vs. 29.282±1.140, P = 0.005). However, there was no significant difference in the genotype and allele frequencies of the microRNA-126 variant (G>A, rs4636297) between cases and controls (P = 0.366). In addition, there was no association between SNP rs4636297 and survival time in NSCLC patients (P = 0.992). And microRNA-126 expression had no significant difference among the three genotype groups (P = 0.972).

Conclusions: Our data indicate that microRNA-126 is a tumor-suppressor gene in NSCLC and low microRNA-126 expression is a unfavorable prognostic factor in NSCLC patients. However, the regulatory mechanism of microRNA-126 remains to be elucidated in different normal and malignant tissues. Therefore, further research is needed to explore the tumor suppressive functions of microRNA-126 in NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Female
  • Gene Expression*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Staging
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Polymorphism, Single Nucleotide
  • Proto-Oncogene Proteins c-akt / metabolism
  • Risk Factors
  • Signal Transduction
  • Xenograft Model Antitumor Assays

Substances

  • MIRN126 microRNA, human
  • MicroRNAs
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt

Grants and funding

This work was supported by National Natural Science Foundation of China (grant number 30800633) and Sichuan Province Science and Technology Foundation for Youths (grant number 09ZQ026-034). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.