MicroRNA-409-3p functions as a tumor suppressor in human lung adenocarcinoma by targeting c-Met

Cell Physiol Biochem. 2014;34(4):1273-90. doi: 10.1159/000366337. Epub 2014 Sep 29.

Abstract

Background/aims: Dysregulation of microRNAs is correlated with tumor development. The aim of this study is to investigate the clinicopathologic and prognostic significance of microRNA (miR)-409-3p and its tumor suppressor roles in lung adenocarcinoma (LAD).

Methods: Quantitative real-time PCR (qRT-PCR) was performed to detect miR-409-3p expression in LAD tissues and corresponding noncancerous tissues. Additionally, the correlations of miR-409-3p expression with clinicopathologic factors and prognosis of patients were statistically analyzed. Next, we investigated whether miR-409-3p could function as a tumor suppressor in LAD cells via regulation of Akt signaling by targeting receptor tyrosine kinase (c-Met).

Results: MiR-409-3p was significantly downregulated in LAD tissues compared with corresponding noncancerous tissues. Low miR-409-3p expression was observed to be significantly correlated with poorer tumor differentiation, advanced pTNM stage and higher incidence of lymph node metastasis. Multivariate Cox regression analyses showed that miR-409-3p expression was an independent prognostic factor for LAD patients. Functional analyses indicated that miR-409-3p could inhibit growth, induce apoptosis, reduce migration and invasion in LAD cells via inactivation of Akt signaling by targeting c-Met.

Conclusions: MiR-409-3p was an independent prognostic factor and functioned as a tumor suppressor in LAD via regulation of Akt signaling by targeting c-Met.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Apoptosis / genetics
  • Cell Differentiation / genetics
  • Cell Line
  • Cell Line, Tumor
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Genes, Tumor Suppressor / physiology*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / pathology
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-met / genetics*
  • Signal Transduction / genetics

Substances

  • MIRN409 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-met
  • Proto-Oncogene Proteins c-akt