The p53/miR-34a/SIRT1 Positive Feedback Loop in Quercetin-Induced Apoptosis
The p53/miR-34a/SIRT1 Positive Feedback Loop in Quercetin-Induced Apoptosis
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槲皮素诱导的细胞凋亡中的 p53/miR-34a/SIRT1 正反馈环
DOI：
10.1159/000374024
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发表时间：
2015-01-01
影响因子：
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通讯作者：
Chen, Zhi
中科院分区：
文献类型：
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作者：
Lou, Guohua;Liu, Yanning;Chen, Zhi
背景：槲皮素的抗肿瘤作用已有报道，但其分子机制尚不清楚。本研究旨在探讨miRNA在槲皮素抗肿瘤作用中的作用。方法：采用基因芯片技术检测槲皮素对HepG 2和Huh 7细胞miRNAs表达的影响。采用xCELLigence、流式细胞术、RT-PCR和Western blot等方法分析细胞增殖、细胞凋亡、细胞周期阻滞、抗肿瘤基因和蛋白表达。结果：经槲皮素处理的HepG 2细胞中miR-34 a表达上调，并呈现野生型p53。抑制miR-34 a后，细胞对槲皮素的敏感性降低，SIRT 1表达上调，而p53乙酰化及相关基因表达下调。结论：miR-34 a在槲皮素抗肝癌作用中起重要作用，miR-34 a可能是p53和SIRT 1之间的一个中间分子，构成p53/miR-34 a/SIRT 1信号反馈环，可增强凋亡信号，显著促进细胞凋亡。
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.