Genome-wide microRNA expression profiling in renal cell carcinoma: significant down-regulation of miR-141 and miR-200c

J Pathol. 2008 Dec;216(4):418-27. doi: 10.1002/path.2437.


We investigated expression profiles of microRNA (miRNA) in renal cell carcinoma [clear cell carcinomas (CCC) and chromophobe renal cell carcinomas (ChCC)] and in normal kidneys by using a miRNA microarray platform which covers a total of 470 human miRNAs (Sanger miRBase release 9.1). Unsupervised hierarchical cluster analysis revealed that CCC and ChCC were separable and that no subgroups were identified in CCCs. We found that 43 miRNAs were differentially expressed between CCC and normal kidney, of which 37 were significantly down-regulated in CCC and the other 6 were up-regulated. We also found that 57 miRNAs were differentially expressed between ChCC and normal kidney, of which 51 were significantly down-regulated in ChCC and the other 6 were up-regulated. Together, these observations indicate that expression of miRNAs tends to be down-regulated in both CCC and ChCC compared with normal kidney. We observed that miR-141 and miR-200c were the most significantly down-regulated miRNAs in CCCs. Indeed, in all cases of CCC analysed, both miR-141 and miR-200c were down-regulated in comparison with normal kidney. Microarray data and quantitative RT-PCR showed that these two miRNAs were expressed concordantly. TargetScan algorithm revealed that ZFHX1B mRNA is a hypothetical target of both miR-141 and -200c. We established by quantitative RT-PCR that, in CCCs in which miR-141 and miR-200c were down-regulated, ZFHX1B, a transcriptional repressor for CDH1/E-cadherin, tended to be up-regulated. Furthermore, we found that overexpression of miR-141 and miR-200c caused down-regulation of ZFHX1B and up-regulation of E-cadherin in two renal carcinoma cell lines, ACHN and 786-O. On the basis of these findings, we suggest that down-regulation of miR-141 and miR-200c in CCCs might be involved in suppression of CDH1/E-cadherin transcription via up-regulation of ZFHX1B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cadherins / genetics
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Down-Regulation*
  • Female
  • Gene Dosage
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic*
  • Genome
  • Homeodomain Proteins / genetics
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • Male
  • MicroRNAs / genetics*
  • Microscopy, Confocal
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Repressor Proteins / genetics
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Zinc Finger E-box Binding Homeobox 2


  • Cadherins
  • Homeodomain Proteins
  • MIRN141 microRNA, human
  • MIRN200 microRNA, human
  • MicroRNAs
  • Repressor Proteins
  • ZEB2 protein, human
  • Zinc Finger E-box Binding Homeobox 2