title: Genistein downregulates onco-miR-1260b and inhibits Wnt-signalling in renal cancer cells.
abstract: BACKGROUND
  Wnt-signalling has an important role in renal cancer and it is modulated by genistein in other cancers. Recently, microRNAs (miRNAs) have emerged as new regulators of gene expression. Thus, we focused on miRNAs to examine the regulatory mechanism of genistein on the Wnt-signalling pathway in renal cell carcinoma (RCC).
  
  
  METHODS
  Initially, we investigated the effect of genistein on Wnt-signalling (TOPflash reporter assay (TCF reporter assays)) in renal cancer cells, and using microarray identified candidate miRNAs whose expression was decreased by genistein. We performed functional analyses and investigated the relationship between miRNA expression and renal cancer patient outcomes. We also did 3'UTR luciferase assays to look at direct miRNA regulation of Wnt-signalling-related genes.
  
  
  RESULTS
  Genistein promoted apoptosis while inhibiting RCC cell proliferation and invasion. Genistein also decreased TCF reporter activity in RCC cells. We found that miR-1260b was highly expressed and significantly downregulated by genistein in RCC cells. The expression of miR-1260b was significantly higher in renal cancer tissues compared with normal, and significantly related to overall shorter survival. In addition, miR-1260b promoted renal cancer cell proliferation and invasion in RCC cells. The 3'UTR luciferase activity of target genes (sFRP1, Dkk2, Smad4) was significantly decreased and their protein expression significantly upregulated in miR-1260b inhibitor-transfected renal cancer cells.
  
  
  CONCLUSIONS
  Our data suggest that genistein inhibited Wnt-signalling by regulating miR-1260b expression in renal cancer cells.
authors.affiliation: Department of Urology, San Francisco Veterans Affairs Medical Center and University of California at San Francisco, San Francisco, CA 94121, USA.
authors.forename: H
authors.initials: H
authors.lastname: Hirata
authors.forename: K
authors.initials: K
authors.lastname: Ueno
authors.forename: K
authors.initials: K
authors.lastname: Nakajima
authors.forename: Z L
authors.initials: ZL
authors.lastname: Tabatabai
authors.forename: Y
authors.initials: Y
authors.lastname: Hinoda
authors.forename: N
authors.initials: N
authors.lastname: Ishii
authors.forename: R
authors.initials: R
authors.lastname: Dahiya
mesh_terms: D000328:Adult; D000368:Aged; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009857:Oncogenes / Q000187:drug effects / Q000235:genetics; D014407:Tumor Cells, Cultured; D060449:Wnt Signaling Pathway / Q000187:drug effects*
chemical_list: D016588:Anticarcinogenic Agents; C582445:MIRN1260 microRNA, human; D035683:MicroRNAs; D019833:Genistein