Berberine-induced tumor suppressor p53 up-regulation gets involved in the regulatory network of MIR-23a in hepatocellular carcinoma

Ning Wang, Meifen Zhu, Xuanbin Wang, Hor-Yue Tan, Sai-wah Tsao, Yibin Feng*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

76 Citations (Scopus)

Abstract

Aim of the study: 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. 

Conclusion: Our study reveals that miR-23a may be involved in regulating the anti-HCC effect of berberine by mediating the regulation of p53.

Original languageEnglish
Pages (from-to)849-857
Number of pages9
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume1839
Issue number9
Early online date2 Jun 2014
DOIs
Publication statusPublished - Sept 2014

Scopus Subject Areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics

User-Defined Keywords

  • Berberine
  • miR-23a
  • p53
  • Tumor growth inhibition
  • Hepatocellular carcinoma

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