组蛋白去乙酰化下调对肾细胞癌BNIP3基因表达的影响

发布时间：2018-04-01 09:41

本文选题：肾细胞癌　切入点：BNIP　出处：《四川大学学报(医学版)》2017年03期

【摘要】：目的探讨肾细胞癌中线粒体促凋亡蛋白BNIP3表达下调机制。方法运用CCK-8法及流式细胞技术检测组蛋白去乙酰化酶抑制剂曲古霉素A(TSA)对肾癌细胞株786-O、ACHN、A498增殖、凋亡的影响;运用实时荧光定量PCR(Q-PCR)和蛋白质免疫印记(Western blot)技术检测TSA对肾癌细胞BNIP3表达的影响;运用染色质免疫沉淀(ChIP)技术检测TSA对肾癌细胞BNIP3基因启动子区组蛋白H3乙酰化状态的影响。结果经TSA处理后,3种肾癌细胞增殖均受到显著抑制(P0.05),细胞早期凋亡明显增加,BNIP3mRNA(P0.05)和蛋白表达水平上调。786-O、ACHN的BNIP3基因启动子区组蛋白H3呈去乙酰化状态,TSA恢复了其乙酰化状态;A498的BNIP3基因启动子区组蛋白H3呈乙酰化状态。结论 BNIP3基因启动子区组蛋白去乙酰化是其在肾癌中表达下调的主要机制,并可能参与了肾癌的发生发展。
[Abstract]:Objective to investigate the down-regulation mechanism of mitochondrial apoptotic protein (BNIP3) expression in renal cell carcinoma (RCC). Methods CCK-8 assay and flow cytometry were used to detect the effect of Tracotomycin (TSA), an inhibitor of histone deacetylase, on the proliferation and apoptosis of renal cell carcinoma cell line 786-OGN A498. The effect of TSA on the expression of BNIP3 in renal cancer cells was detected by real-time fluorescence quantitative PCRQ-PCR and Western blot technique. Chromatin immunoprecipitation technique was used to detect the effect of TSA on the acetylation of histone H3 in the promoter of BNIP3 gene in renal cancer cells. Results after TSA treatment, the proliferation of three kinds of renal cell carcinoma cells was significantly inhibited, and the early apoptosis of the cells was observed. BNIP3 promoter H3 was deacetylated and the BNIP3 promoter H3 of A498 was acetylated. Conclusion BNIP3 gene promoter H3 is acetylated. Deacetylation of motile histone is the main mechanism of its down-regulation in renal cell carcinoma. And may be involved in the development of renal cell carcinoma.
【作者单位】：四川大学华西医院泌尿外科;四川大学华西医院泌尿外科研究所;四川大学华西医院病理研究室;
【分类号】：R737.11

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