Clinic significance of microRNA-99a expression in human lung adenocarcinoma

J Surg Oncol. 2013 Sep;108(4):248-55. doi: 10.1002/jso.23381. Epub 2013 Jul 24.

Abstract

Background: The purpose of this study was to investigate the clinical significance of microRNA-99a expression in lung adenocarcinoma.

Methods: qRT-PCR assay was performed to detect miR-99a expression in lung adenocarcinoma cells or tissues. The correlations of miR-99a expression with clinicopathological factors and prognosis of lung adenocarcinoma patients were analyzed. The effects of miR-99a expression on growth and apoptosis of lung adenocarcinoma cell line and its potential target gene were determined by MTT, flow cytometry, luciferase reporter, and Western blot assays.

Results: The relative miR-99a expression in lung adenocarcinoma cells was significantly lower than that in normal lung bronchial epithelium cell line. Also, miR-99a expression in lung adenocarcinoma tissues was significantly lower than that in corresponding nontumor tissues. Low miR-99a expression was found to be closely correlated with advanced clinical stage and lymph node metastasis. Kaplan-Meier survival and Cox regression analyses showed that the status of miR-99a expression was an independent prognosis factor for lung adenocarcinoma patients. Functional analyses showed that upregulation of miR-99a could inhibit growth and induce apoptosis in lung adenocarcinoma cells by targeting mTOR.

Conclusion: Low MiR-99a expression was a poor prognostic factor for patients with lung adenocarcinoma, and miR-99a functions as a tumor suppressor by targeting mTOR.

Keywords: lung adenocarcinoma; mTOR; microRNA-99a; prognosis; qRT-PCR.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology*
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • Apoptosis
  • Cell Line, Tumor
  • Female
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Male
  • MicroRNAs / analysis
  • MicroRNAs / physiology*
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Real-Time Polymerase Chain Reaction
  • TOR Serine-Threonine Kinases / analysis
  • TOR Serine-Threonine Kinases / genetics

Substances

  • MIRN99 microRNA, human
  • MicroRNAs
  • MTOR protein, human
  • TOR Serine-Threonine Kinases