Epithelial-mesenchymal transition-related microRNA-200s regulate molecular targets and pathways in renal cell carcinoma

J Hum Genet. 2013 Aug;58(8):508-16. doi: 10.1038/jhg.2013.31. Epub 2013 May 2.


Our recent studies of microRNA (miRNA) expression signatures demonstrated that the epithelial-mesenchymal transition (EMT)-related microRNA-200 family (miR-200s: miR-200a/b/c, miR-141 and miR-429) were significantly downregulated in renal cell carcinoma (RCC) and putative tumor-suppressive miRNAs in RCC. In this study, our aim was to investigate the functional significance of the miR-200s in cancer cells and to identify novel miR-200s-regulated molecular targets and pathways in RCC. Expression levels of all the miR-200s members were significantly downregulated in human RCC tissues compared with normal renal tissues. Restoration of mature miR-200s in RCC cell line resulted in significant inhibition of cell proliferation and migration, suggesting that miR-200s function as tumor suppressors in RCC. Furthermore, we utilized gene expression analysis and in silico database analysis to identify miR-200s-regulated molecular targets and pathways in RCC. The miR-200s was categorized into two groups, according to their seed sequences, miR-200b/c/429 and miR-200a/141. Our data demonstrated that the 'Focal adhesion' and 'ErbB signaling' pathways were significantly regulated by miR-200b/c/429 and miR-200a/141, respectively. The identification of novel tumor-suppressive miR-200s-regulated molecular targets and pathways has provided new insights into RCC oncogenesis and metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Chromosomes, Human / genetics
  • Down-Regulation / genetics
  • Epithelial-Mesenchymal Transition / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genes, Neoplasm / genetics
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Molecular Sequence Data
  • Sequence Alignment
  • Signal Transduction / genetics*
  • Transfection


  • MIRN141 microRNA, human
  • MIRN200 microRNA, human
  • MIRN429 microRNA, human
  • MicroRNAs