MiR-761 Promotes Progression and Metastasis of Non-Small Cell Lung Cancer by Targeting ING4 and TIMP2

Cell Physiol Biochem. 2015;37(1):55-66. doi: 10.1159/000430333. Epub 2015 Aug 12.

Abstract

Background/aims: The aim of this study was to investigate the role of microRNA miR-761 in the progression and metastasis of non-small cell lung cancer (NSCLC), and the mechanisms by which miR-761 regulates cell proliferation and metastatic activity of NSCLC cell lines.

Methods: Quantitative real-time PCR (qRT-PCR) was used to assess miR-761 expression in NSCLC serum and tissue. MTT, wound healing, and transwell assays were performed to examine the role of miR-761 in regulation of cell proliferation and metastatic activity in NSCLC cell lines. In addition, the correlations of miR-761 expression with clinical-pathologic factors were statistically analyzed. Finally, we investigated whether miR-761 promotes proliferation and metastasis in NSCLC cell lines by targeting ING4 (inhibitor of growth family, member 4) and TIMP2 (tissue inhibitor of metalloproteinase 2).

Results: MiR-761 was significantly upregulated in both NSCLC serum and tissues as compared to normal participants and paired noncancerous tissues respectively. Ectopic expression of miR-761 promoted cell proliferation and metastasis in H460 cells, while miR-761 inhibitor reduced proliferation rates and metastasis in H23 cells. Furthermore, luciferase reporter assay and functional analyses indicated that miR-761 directly targeted ING4 and TIMP2.

Conclusion: miR-761 promotes progression and metastasis of NSCLC by targeting ING4 and TIMP2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Cycle Proteins / genetics*
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Homeodomain Proteins / genetics*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / pathology
  • Tissue Inhibitor of Metalloproteinase-2 / genetics*
  • Tumor Suppressor Proteins / genetics*
  • Up-Regulation / genetics

Substances

  • Cell Cycle Proteins
  • Homeodomain Proteins
  • ING4 protein, human
  • MicroRNAs
  • TIMP2 protein, human
  • Tumor Suppressor Proteins
  • Tissue Inhibitor of Metalloproteinase-2