title: TGF-beta induced RBL2 expression in renal cancer cells by down-regulating miR-93.
abstract: OBJECTIVE
  TGF-beta can induce G1 arrest via many mechanisms including up-regulating p21, p27, and Rb. However, as the member of Rb family, whether RBL2 is induced by TGF-beta treatment remains exclusive.
  
  
  METHODS
  The expression of RBL2 and miR-93 after TGF-beta treatment was determined by quantitative real-time PCR and western blot. The growth of renal cancer cells was determined by CCK-8 assays and cell cycle was determined by PI staining. The binding of miR-93 on RBL2 3'-UTR was determined by double luciferase system.
  
  
  RESULTS
  In renal cancer cells, TGF-beta treatment induced expression of RBL2 in a time- and concentration-dependent manner, and RBL2 mediated TGF-beta induced growth inhibition and cell cycle arrest in renal cancer cells. Furthermore, we found that miR-93 directly targeted RBL2 by binding to its 3'-UTR in renal cancer cells. Over-expression of miR-93 significantly reduced the expression of RBL2, whereas knock down of miR-93 up-regulated the expression of RBL2. More importantly, TGF-beta treatment inhibited miR-93 expression, which resulted in up-regulation of RBL2 after TGF-beta treatment.
  
  
  CONCLUSIONS
  TGF-beta induced RBL2 expression through down-regulating miR-93 in renal cancer cells. The newly identified TGF-beta/miR-93/RBL2 signal pathway reveals a new mechanism of TGF-beta induced growth arrest in renal cancer.
authors.affiliation: Department of Urology, Tangshan Gongren Hospital, Hebei Medical University, No. 27, Wenhua Road, Lubei District, Tangshan, 063000, China.
authors.forename: J
authors.initials: J
authors.lastname: Shi
authors.forename: Y
authors.initials: Y
authors.lastname: Zhuang
authors.forename: X K
authors.initials: XK
authors.lastname: Liu
authors.forename: Y X
authors.initials: YX
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D050717:Retinoblastoma-Like Protein p130 / Q000096:biosynthesis*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C543350:MIRN93 microRNA, human; D035683:MicroRNAs; C493837:RBL2 protein, human; D050717:Retinoblastoma-Like Protein p130; D016212:Transforming Growth Factor beta