Tumor suppressive microRNA-200a inhibits renal cell carcinoma development by directly targeting TGFB2

Tumour Biol. 2015 Sep;36(9):6691-700. doi: 10.1007/s13277-015-3355-9. Epub 2015 Mar 27.

Abstract

A large body of evidence indicates that microRNAs play a critical role in tumor initiation and progression by negatively regulating oncogenes or tumor suppressor genes. Here, we report that the expression of miR-200a was notably downregulated in 45 renal cell carcinoma (RCC) samples. Restoration of miR-200a suppressed cell proliferation, migration, and invasion in two RCC cell lines. Furthermore, we used an epithelial-to-mesenchymal transition PCR array to explore the putative target genes of miR-200a. By performing quantitative real-time PCR, ELISA, and luciferase reporter assays, transforming growth factor beta2 (TGFB2) was validated as a direct target gene of miR-200a. Moreover, siRNA-mediated knockdown of TGFB2 partially phenocopied the effect of miR-200a overexpression. These results suggest that miR-200a suppresses RCC development via directly targeting TGFB2, indicating that miR-200a may present a novel target for diagnostic and therapeutic strategies in RCC.

Keywords: Renal cell carcinoma; TGFB2; Tumor suppressor; miR-200a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic
  • Gene Knockout Techniques
  • Humans
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • RNA, Small Interfering / genetics
  • Transforming Growth Factor beta2 / biosynthesis*
  • Transforming Growth Factor beta2 / genetics

Substances

  • MIRN200 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • TGFB2 protein, human
  • Transforming Growth Factor beta2