title: The functional significance of miR-1 and miR-133a in renal cell carcinoma.
abstract: OBJECTIVE
  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.
authors: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors: Kazumori
authors: K
authors: Kawakami
authors: Hideki
authors: H
authors: Enokida
authors: Takeshi
authors: T
authors: Chiyomaru
authors: Shuichi
authors: S
authors: Tatarano
authors: Hirofumi
authors: H
authors: Yoshino
authors: Ichiro
authors: I
authors: Kagara
authors: Takenari
authors: T
authors: Gotanda
authors: Tokushi
authors: T
authors: Tachiwada
authors: Kenryu
authors: K
authors: Nishiyama
authors: Nijiro
authors: N
authors: Nohata
authors: Naohiko
authors: N
authors: Seki
authors: Masayuki
authors: M
authors: Nakagawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C544547:MIRN1 microRNA, human; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D008840:Microfilament Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C051615:transgelin