title: Negative feedback between TAp63 and Mir-133b mediates colorectal cancer suppression.
abstract: BACKGROUND
  TAp63 is known as the most potent transcription activator and tumor suppressor. microRNAs (miRNAs) are increasingly recognized as essential components of the p63 pathway, mediating downstream post-transcriptional gene repression. The aim of present study was to investigate a negative feedback loop between TAp63 and miR-133b.
  
  
  RESULTS
  Overexpression of TAp63 inhibited HCT-116 cell proliferation, apoptosis and invasion via miR-133b. Accordingly, miR-133b inhibited TAp63 expression through RhoA and its downstream pathways. Moreover, we demonstrated that TAp63/miR-133b could inhibit colorectal cancer proliferation and metastasis in vivo and vitro.
  
  
  METHODS
  We evaluated the correlation between TAp63 and miR-133b in HCT-116 cells and investigated the roles of the TAp63/miR-133b feedback loop in cell proliferation, apoptosis and metastasis via MTT, flow cytometry, Transwell, and nude mouse xenograft experiments. The expression of TAp63, miR-133b, RhoA, α-tubulin and Akt was assessed via qRT-PCR, western blot and immunofluorescence analyses. miR-133b target genes were identified through luciferase reporter assays.
  
  
  CONCLUSIONS
  miR-133b plays an important role in the anti-tumor effects of TAp63 in colorectal cancer. miR-133b may represent a tiemolecule between TAp63 and RhoA, forming a TAp63/miR-133b/RhoA negative feedback loop, which could significantly inhibit proliferation, apoptosis and metastasis.
authors.affiliation: Department of Gastrointestinal and Thyroid Surgery, The Third Xiang Ya Hospital of Central South University, Changsha, Hunan 410013, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Gastrointestinal and Thyroid Surgery, The Third Xiang Ya Hospital of Central South University, Changsha, Hunan 410013, P. R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Gastrointestinal and Thyroid Surgery, The Third Xiang Ya Hospital of Central South University, Changsha, Hunan 410013, P. R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal and Thyroid Surgery, The Third Xiang Ya Hospital of Central South University, Changsha, Hunan 410013, P. R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Gao
authors.affiliation: Department of Gastrointestinal and Thyroid Surgery, The Third Xiang Ya Hospital of Central South University, Changsha, Hunan 410013, P. R. China.
authors.forename: Gui
authors.initials: G
authors.lastname: Hu
authors.affiliation: Department of Gastrointestinal and Thyroid Surgery, The Third Xiang Ya Hospital of Central South University, Changsha, Hunan 410013, P. R. China.
authors.forename: Yihang
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Gastrointestinal and Thyroid Surgery, The Third Xiang Ya Hospital of Central South University, Changsha, Hunan 410013, P. R. China.
authors.forename: Changwei
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of Gastrointestinal and Thyroid Surgery, The Third Xiang Ya Hospital of Central South University, Changsha, Hunan 410013, P. R. China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000473:pathology* / Q000517:prevention & control; D045325:HCT116 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000502:physiology
chemical_list: C548234:MIRN133 microRNA, human; D035683:MicroRNAs; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C066737:RHOA protein, human; D020742:rhoA GTP-Binding Protein
keywords: TAp63; metastasis; miR-133b; negative feedback; proliferation