miRNA-221 Promotes Proliferation, Migration and Invasion by Targeting TIMP2 in Renal Cell Carcinoma

Int J Clin Exp Pathol. 2015 May 1;8(5):5224-9. eCollection 2015.

Abstract

Introduction: MicroRNAs (miRNAs) play important roles in tumorigenesis. In this study, we investigated the role of miR-221 in the development and progression of clear cell renal cell carcinoma (ccRCC).

Methods: Quantitative real-time PCR (qRT-PCR) was used to measure the expression level of miR-221 in ccRCC tissues and cell lines. Then, we investigated the role of miR-221 to determine its potential roles on renal cancer cell proliferation, migration and invasion in vitro. A luciferase reporter assay was conducted to confirm the target gene of miR-221 and the results were validated in renal cancer cells.

Results: In the present study, we found that miR-221 was significantly increased in ccRCC tissues and cell lines. Knocked-down expression of miR-221 remarkably inhibited cell proliferation, migration and invasion of renal cancer cells. Moreover, at the molecular level, our results suggested that TIMP2 as a direct target of miR-221 through which miR-221 promoted tumor cell proliferation, migration and invasion.

Conclusions: These findings suggested that miR-221 play an oncogenic role in the renal cancer cell proliferation, migration and invasion by directly inhibiting the tumor suppressor TIMP2, indicating miR-221 act as a potential new therapeutic target for the treatment of ccRCC.

Keywords: Clear cell renal cell carcinoma; TIMP2; miR-221.

MeSH terms

  • 3' Untranslated Regions
  • Binding Sites
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation*
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Genes, Reporter
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • Luciferases / genetics
  • Luciferases / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Oncogenes
  • RNA Interference
  • Signal Transduction
  • Tissue Inhibitor of Metalloproteinase-2 / genetics
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism*
  • Transfection

Substances

  • 3' Untranslated Regions
  • MIRN221 microRNA, human
  • MicroRNAs
  • TIMP2 protein, human
  • Tissue Inhibitor of Metalloproteinase-2
  • Luciferases