MicroRNA-429 suppresses cell proliferation, epithelial-mesenchymal transition, and metastasis by direct targeting of BMI1 and E2F3 in renal cell carcinoma

Urol Oncol. 2015 Jul;33(7):332.e9-18. doi: 10.1016/j.urolonc.2015.03.016. Epub 2015 May 4.

Abstract

Background: MicroRNA-429 (miR-429), a short noncoding RNA belonging to the miR-200 superfamily, plays a crucial role in tumorigenesis and tumor progression. It also acts as a modulator of epithelial-to-mesenchymal transition, a cell development regulating process that affects tumor development and metastasis. The aim of this study was to investigate the potential role of miR-429 in regulating growth and metastasis of renal cell carcinoma.

Methods: miR-429 expression was stably up-regulated or down-regulated in the renal cell carcinoma ACHN and A498 cell lines, and cell proliferation and metastasis were assessed.

Results: miR-429 overexpression inhibited cell proliferation, colony formation, migration, and invasion. Suppression of endogenous miR-429 promoted cell growth and metastasis. miR-429 was shown to directly target the 3' untranslated regions of B-cell-specific Moloney murine leukemia virus insertion site 1 (BMI1) and E2F transcription factor 3 (E2F3) transcripts, regulating their expression, as well as that of the downstream epithelial-to-mesenchymal transition markers E-cadherin, N-cadherin, vimentin, p14, and p16.

Conclusions: These results revealed a tumor suppressive role for miR-429 in renal cell carcinoma through directly targeting BMI1 and E2F3.

Keywords: BMI1; E2F3; Renal carcinoma cells; miR-429.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / secondary*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation / physiology
  • DNA Primers / chemistry
  • E2F3 Transcription Factor / metabolism*
  • Epithelial-Mesenchymal Transition*
  • Gene Expression Regulation
  • Genetic Vectors
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology*
  • MicroRNAs / physiology*
  • Plasmids
  • Polycomb Repressive Complex 1 / metabolism*
  • Real-Time Polymerase Chain Reaction

Substances

  • BMI1 protein, human
  • DNA Primers
  • E2F3 Transcription Factor
  • E2F3 protein, human
  • MIRN429 microRNA, human
  • MicroRNAs
  • Polycomb Repressive Complex 1