槲皮素诱导凋亡过程中的p53/miR-34a/SIRT1正反馈环
The p53/miR-34a/SIRT1 Positive Feedback Loop in Quercetin-Induced Apoptosis.
作者信息
Lou Guohua, Liu Yanning, Wu Shanshan, Xue Jihua, Yang Fan, Fu Haijing, Zheng Min, Chen Zhi
机构信息
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University. Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
出版信息
Cell Physiol Biochem. 2015;35(6):2192-202. doi: 10.1159/000374024. Epub 2015 Apr 7.
BACKGROUND
The anti-tumor effects of quercetin have been reported, but the underlying molecular mechanisms remain to be elucidated. The aim of present study was to explore the role of miRNA in the anticancer effects of quercetin.
METHODS
The differential miRNAs expression between the HepG2 and Huh7 cells treated by quercetin were detected by microarray. The xCELLigence, Flow cytometry, RT-PCR and Western blot were used to analyze the cell proliferation, cell apoptosis, cell cycle arrest, anti-tumor genes, and protein expression.
RESULTS
miR-34a was up-regulated in HepG2 cells treated by quercetin exhibiting wild-type p53. When inhibiting the miR-34a, the sensitivity of the cells to quercetin decreased and the expression of the SIRT1 was up-regulated, but the acetylation of p53 and the expression of some genes related to p53 down-regulated.
CONCLUSION
miR-34a plays an important role in the anti-tumor effects of querctin in HCC, miR-34a may be a tiemolecule between the p53 and SIRT1 and is composed of a p53/miR-34a/SIRT1 signal feedback loop, which could enhance apoptosis signal and significantly promote cell apoptosis.
背景
槲皮素的抗肿瘤作用已有报道，但其潜在的分子机制仍有待阐明。本研究旨在探讨miRNA在槲皮素抗癌作用中的作用。
方法
通过微阵列检测槲皮素处理的HepG2和Huh7细胞之间的差异miRNA表达。使用xCELLigence、流式细胞术、RT-PCR和蛋白质印迹分析细胞增殖、细胞凋亡、细胞周期阻滞、抗肿瘤基因和蛋白质表达。
结果
在表现出野生型p53的槲皮素处理的HepG2细胞中，miR-34a上调。当抑制miR-34a时，细胞对槲皮素的敏感性降低，SIRT1的表达上调，但p53的乙酰化和一些与p53相关的基因的表达下调。
结论
miR-34a在槲皮素对肝癌的抗肿瘤作用中起重要作用，miR-34a可能是p53和SIRT1之间的一个分子，由p53/miR-34a/SIRT1信号反馈环组成，可增强凋亡信号并显著促进细胞凋亡。
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