title: Berberine-induced tumor suppressor p53 up-regulation gets involved in the regulatory network of MIR-23a in hepatocellular carcinoma.
abstract: OBJECTIVE
  To investigate the involvement of p53 in the regulatory network of microRNA-23a (miR-23a) in berberine-treated hepatocellular carcinoma (HCC) cells.
  
  
  METHODS
  The biogenesis of miR-23a upon berberine treatment was monitored by detecting the transcript expression of primary precursor, precursor and mature forms of miR-23a. Protein expression was detected with immunoblotting. The binding capacity between p53 and chromatin DNA was determined by chromatin immunoprecipitation. The role of miR-23a in mediating suppression of HCC by berberine was determined both in vitro and in vivo.
  
  
  RESULTS
  miR-23a was up-regulated upon berberine treatment in human HCC cells, and berberine could increase the expression of primary precursor, precursor and mature forms of miR-23a. The up-regulation of miR-23a by berberine is p53-dependent. Inhibition of p53 expression and activity could block the up-regulation of miR-23a induced by berberine. Furthermore, berberine-induced miR-23a expression may mediate the transcription activation of p53-related tumor suppressive genes p21 and GADD45α. Inhibition of miR-23a abolishes the binding of p53 onto chromatin and attenuates transcription activation of p21 and GADD45α. Target prediction and experimental validation demonstrate that berberine-induced miR-23a may target to Nek6 to suppress its expression. Berberine-induced G2/M cell cycle arrest in HCC was attenuated when miR-23a was inhibited. Berberine-induced cell death and in vivo tumor growth inhibition are attenuated upon inhibition of miR-23a.
  
  
  CONCLUSIONS
  Our study reveals that miR-23a may be involved in regulating the anti-HCC effect of berberine by mediating the regulation of p53.
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, PR China.
authors.forename: Meifen
authors.initials: M
authors.lastname: Zhu
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, PR China; Laboratory of Chinese Herbal Pharmacology, Renmin Hospital, School of Pharmacy, Hubei University of Medicine, 442000, PR China.
authors.forename: Xuanbin
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, PR China.
authors.forename: Hor-Yue
authors.initials: HY
authors.lastname: Tan
authors.affiliation: Department of Anatomy, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, PR China.
authors.forename: Sai-Wah
authors.initials: SW
authors.lastname: Tsao
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, PR China. Electronic address: yfeng@hku.hk.
authors.forename: Yibin
authors.initials: Y
authors.lastname: Feng
mesh_terms: D001599:Berberine / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D053263:Gene Regulatory Networks; D016158:Genes, p53; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics* / Q000502:physiology; D015854:Up-Regulation
chemical_list: C552430:MIRN23a microRNA, human; D035683:MicroRNAs; D001599:Berberine
keywords: Berberine; Hepatocellular carcinoma; Tumor growth inhibition; miR-23a; p53