The functional significance of miR-1 and miR-133a in renal cell carcinoma

Eur J Cancer. 2012 Apr;48(6):827-36. doi: 10.1016/j.ejca.2011.06.030.


Purpose: The aim of this study was to find a novel molecular network involved in renal cell carcinoma (RCC) development through investigating the functions of miR-1 and miR-133a and their target genes.

Methods: We checked the expression levels of miR-1 and miR-133a in RCC cell lines and specimens (N=40) using real time RT-PCR. MiR-1 and miR-133a transfectants were subjected to a gain-of-function study to identify the functions of the miRNAs. To find the target genes of the miRNAs, we analysed the gene expression profile of their transfectants and performed a luciferase reporter assay. mRNA expression levels of the candidate target gene in the clinical specimens were examined, and loss-of-function studies were performed.

Results: The expression levels of miR-1 and miR-133a were significantly suppressed in RCC cell lines and specimens. Ectopic restoration of miR-1 and miR-133a showed significant inhibition of cell proliferation and invasion, and moreover, revealed induction of apoptosis and cell cycle arrest. The luciferase assay revealed transgelin-2 (TAGLN2), selected as a target gene for miR-1 and miR-133a on the basis of the gene expression profile, to be directly regulated by both miR-1 and miR-133a. The loss-of-function studies showed significant inhibitions of cell proliferation and invasion in the si-TAGLN2 transfectant. The expression level of TAGLN2 mRNA was significantly up-regulated in the RCC specimens; in addition, there was a statistically significant inverse correlation between TAGLN2 and miR-1 and miR-133a expression.

Conclusions: Our data indicate that up-regulation of the oncogenic TAGLN2 was due to down-regulation of tumour-suppressive miR-1 and miR-133a in human RCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis / drug effects
  • Blotting, Western
  • Carcinoma, Renal Cell / metabolism*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Flow Cytometry
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Kidney Neoplasms / metabolism*
  • Male
  • MicroRNAs / metabolism*
  • Microfilament Proteins / metabolism*
  • Middle Aged
  • Muscle Proteins / metabolism*
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction


  • MIRN1 microRNA, human
  • MIRN133 microRNA, human
  • MicroRNAs
  • Microfilament Proteins
  • Muscle Proteins
  • RNA, Messenger
  • transgelin