TY - JOUR
T1 - Berberine-induced tumor suppressor p53 up-regulation gets involved in the regulatory network of MIR-23a in hepatocellular carcinoma
AU - Wang, Ning
AU - Zhu, Meifen
AU - Wang, Xuanbin
AU - Tan, Hor-Yue
AU - Tsao, Sai-wah
AU - Feng, Yibin
N1 - Funding Information:
This work was financially supported in part by grants from the research council of the University of Hong Kong (Project Codes: 10401764 , 201309176224 ), The Research Grant Committee ( RGC ) of Hong Kong SAR of China (RGC General Research Fund, Project Code: 10500362 ) and Wong's donation for modern oncology of Chinese Medicine (Project Code: 20006276 ). The authors are grateful to the support of Professors Yao Tong, Yung-Chi Cheng and Allan SY Lau. The authors would like to express thanks to Ms Oi Yee Chow, Ms Cindy Lee, Mr. Keith Wong, and Mr. Freddy Tsang for their technical support.
PY - 2014/9
Y1 - 2014/9
N2 - 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.
AB - 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.
KW - Berberine
KW - miR-23a
KW - p53
KW - Tumor growth inhibition
KW - Hepatocellular carcinoma
UR - http://www.scopus.com/inward/record.url?scp=84904431496&partnerID=8YFLogxK
U2 - 10.1016/j.bbagrm.2014.05.027
DO - 10.1016/j.bbagrm.2014.05.027
M3 - Journal article
C2 - 24942805
AN - SCOPUS:84904431496
SN - 1874-9399
VL - 1839
SP - 849
EP - 857
JO - Biochimica et Biophysica Acta - Gene Regulatory Mechanisms
JF - Biochimica et Biophysica Acta - Gene Regulatory Mechanisms
IS - 9
ER -
