MicroRNA-449a is downregulated in non-small cell lung cancer and inhibits migration and invasion by targeting c-Met

PLoS One. 2013 May 29;8(5):e64759. doi: 10.1371/journal.pone.0064759. Print 2013.

Abstract

MicroRNA-449a is expressed at a low level in several tumors and cancer cell lines, and induces G1 arrest, apoptosis, and senescence. To identify the function of miR-449a in non-small cell lung cancer (NSCLC), we discussed the potential relevance of miR-449a to clinicopathological characteristics and prognosis in NSCLC. We also investigated the impact of miR-449a on migration and invasion in NSCLC cells. The expression of miR-449a in NSCLC tissues and cell lines was detected using RT-qPCR. In vitro, gain-of-function, loss-of-function experiments, and fluorescence assays were performed to identify the potential target of miR-449a and the function of miR-449a in NSCLC cells. MiR-449a was downregulated in both NSCLC tissues and cell lines. Moreover, a low expression level of miR-449a appeared to be correlated with lymph node metastasis and poor survival. In vitro, miR-449 regulated cell migration and invasion in NSCLC cells as a potential tumor suppressor, at least in part by targeting c-Met. Furthermore, reciprocal expression of miR-449a and c-Met was shown in NSCLC tissue samples. This study indicates that miR-449a might be associated with NSCLC progression, and suggests a crucial role for miR-449a in NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adult
  • Aged
  • Base Sequence
  • Blotting, Western
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line
  • Cell Movement / genetics*
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lymphatic Metastasis
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • Proportional Hazards Models
  • Proto-Oncogene Proteins c-met / genetics*
  • Proto-Oncogene Proteins c-met / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / statistics & numerical data
  • Young Adult

Substances

  • 3' Untranslated Regions
  • MIRN449 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-met

Grants and funding

This work was supported by the National Science Foundation of China (No. 30972967) grants, Specialized Research Fund for the Doctoral Program of Higher Education (No. 20092104110018), Program for Liaoning Excellent Talents in University, Liaoning Provincial Natural Science Foundation (No. 20102122), and Shenyang Science and Technology Program (F10-149-9-41). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.