Epigenetic mediated zinc finger protein 671 downregulation promotes cell proliferation and tumorigenicity in nasopharyngeal carcinoma by inhibiting cell cycle arrest.
Epigenetic mediated zinc finger protein 671 downregulation promotes cell proliferation and tumorigenicity in nasopharyngeal carcinoma by inhibiting cell cycle arrest.
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表观遗传介导的锌指蛋白671下调通过抑制细胞周期阻滞促进鼻咽癌细胞增殖和致瘤性
DOI：
10.1186/s13046-017-0621-2
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发表时间：
2017-10-19
期刊：
影响因子：
--
通讯作者：
Sun Y
中科院分区：
文献类型：
--
作者：
Zhang J;Wen X;Liu N;Li YQ;Tang XR;Wang YQ;He QM;Yang XJ;Zhang PP;Ma J;Sun Y
遗传异常在鼻咽癌（NPC）中起重要作用，然而，与异常细胞增殖相关的表观遗传改变尚不清楚。方法采用亚硫酸盐焦磷酸测序法检测znf671在鼻咽癌组织和细胞系中的表观遗传变化。采用实时荧光定量PCR和western blotting检测锌指蛋白671 （ZNF671）在鼻咽癌细胞系和临床组织中的表达。然后，我们建立了稳定过表达znf671和敲低znf671表达的鼻咽癌细胞系，探索其在鼻咽癌中的体外和体内功能。此外，我们通过基因集富集分析、流式细胞术和western blotting鉴定有丝分裂纺锤体和G2/M检查点通路下游基因来研究znf671的潜在机制。结果znf671在鼻咽癌组织和细胞系中高甲基化。znf671在鼻咽癌组织和细胞系中mRNA和蛋白表达下调，经去甲基化剂5-aza-2′-脱氧胞苷处理后mRNA表达上调。znf671过表达抑制鼻咽癌细胞体外增殖和集落形成使用siRNA沉默znf671具有相反的效果。此外，过表达znf671可降低异种移植模型鼻咽癌细胞的体内致瘤性。机制研究表明，过表达znf671通过上调p21，下调cyclin D1和c-myc诱导鼻咽癌细胞S期阻滞。结论遗传介导的锌指蛋白671下调通过抑制鼻咽癌细胞周期阻滞促进细胞增殖，增强致瘤性，可能是一个新的潜在治疗靶点。
BackgroundEpigenetic abnormalities play important roles in nasopharyngeal cancer (NPC), however, the epigenetic changes associated with abnormal cell proliferation remain unclear.MethodsWe detected epigenetic change ofZNF671in NPC tissues and cell lines by bisulfite pyrosequencing. We evaluated zinc finger protein 671 (ZNF671) expression in NPC cell lines and clinical tissues using real-time PCR and western blotting. Then, we established NPC cell lines that stably overexpressedZNF671and knocked downZNF671expression to explore its function in NPC in vitro and in vivo. Additionally, we investigated the potential mechanism ofZNF671by identifying the mitotic spindle and G2/M checkpoint pathways pathway downstream genes using gene set enrichment analysis, flow cytometry and western blotting.ResultsZNF671was hypermethylated in NPC tissues and cell lines. The mRNA and protein expression ofZNF671was down-regulated in NPC tissues and cell lines and the mRNA expression could be upregulated after the demethylation agent 5-aza-2′-deoxycytidine treatment. Overexpression ofZNF671suppressed NPC cell proliferation and colony formation in vitro; silencingZNF671using a siRNA had the opposite effects. Additionally, overexpression ofZNF671reduced the tumorigenicity of NPC cells in xenograft model in vivo. The mechanism study determined that overexpressingZNF671induced S phase arrest in NPC cells by upregulating p21 and downregulating cyclin D1 and c-myc.ConclusionsEpigenetic mediated zinc finger protein 671 downregulation promotes cell proliferation and enhances tumorigenicity by inhibiting cell cycle arrest in NPC, which may represent a novel potential therapeutic target.
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影响因子：
3.8
作者：
Ngollo M;Lebert A;Daures M;Judes G;Rifai K;Dubois L;Kemeny JL;Penault-Llorca F;Bignon YJ;Guy L;Bernard-Gallon D
通讯作者：
Bernard-Gallon D
影响因子：
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作者：
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通讯作者：
Ghaffari, Seyed H.
影响因子：
2.6
作者：
Sak, Ali;Kuebler, Dennis;Stuschke, Martin
通讯作者：
Stuschke, Martin
影响因子：
11.2
作者：
Cheng, Yingduan;Geng, Hua;Tao, Qian
通讯作者：
Tao, Qian
HOPX 高甲基化通过激活鼻咽癌中的 SNAIL 转录促进转移。
影响因子：
16.6
作者：
Ren X;Yang X;Cheng B;Chen X;Zhang T;He Q;Li B;Li Y;Tang X;Wen X;Zhong Q;Kang T;Zeng M;Liu N;Ma J
通讯作者：
Ma J