Cytochrome b5 reductase 2 is a novel candidate tumor suppressor gene frequently inactivated by promoter hypermethylation in human nasopharyngeal carcinoma.
Cytochrome b5 reductase 2 is a novel candidate tumor suppressor gene frequently inactivated by promoter hypermethylation in human nasopharyngeal carcinoma.
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细胞色素 b5 还原酶 2 是一种新型候选抑癌基因，在人鼻咽癌中经常因启动子高甲基化而失活
DOI：
10.1007/s13277-013-1497-1
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发表时间：
2014-04
期刊：
影响因子：
--
通讯作者：
Zeng, Xianjie
中科院分区：
文献类型：
--
作者：
Xiao, Xue;Zhao, Weilin;Tian, Fangyun;Zhou, Xiaoying;Zhang, Jinyan;Huang, Tingting;Hou, Bo;Du, Chunping;Wang, Shumin;Mo, Yingxi;Yu, Nana;Zhou, Shiping;You, Jinping;Zhang, Zhe;Huang, Guangwu;Zeng, Xianjie
细胞色素b5还原酶2 （CYB5R2）是黄蛋白吡啶核苷酸细胞色素还原酶家族的一员，与许多生理反应有关。然而，其在癌症，特别是鼻咽癌（NPC）中的作用尚未得到解决。在这里，我们研究了鼻咽癌衍生细胞系和肿瘤活检中CYB5R2的转录水平和启动子甲基化状态，并通过实验研究了它作为肿瘤抑制基因的作用。我们发现CYB5R2转录水平在鼻咽癌细胞系和肿瘤活检中降低。CYB5R2启动子超甲基化在所有6个测试的鼻咽癌细胞系和84%的原发性鼻咽癌活检中检测到，但在正常鼻咽癌上皮中未发现。临床上CYB5R2甲基化与鼻咽癌患者淋巴结转移相关（P < 0.05）。甲基转移酶抑制剂5-aza-2′-脱氧胞苷能在体外恢复鼻咽癌细胞株内源性CYB5R2的表达。CYB5R2异位表达对鼻咽癌细胞的增殖、克隆性和迁移有抑制作用。此外，裸鼠体内实验表明，CYB5R2的异位表达降低了CYB5R2阴性鼻咽癌细胞的致瘤性。总的来说，这些发现表明CYB5R2可能是一个功能性的肿瘤抑制基因，在鼻咽癌中经常因其启动子的高甲基化而失活。我们在这里报道了鼻咽癌肿瘤活检中一个关键酶CYB5R2的表观遗传下调的第一个例子，CYB5R2负责环境致癌物的解毒。我们提出了在未来利用CYB5R2启动子甲基化作为鼻咽癌诊断生物标志物的可能性。
Cytochrome b5 reductase 2 (CYB5R2), a member of the flavoprotein pyridine nucleotide cytochrome reductase family, is associated with a number of physiological reactions. However, its role in cancer, especially nasopharyngeal carcinoma (NPC), has not been addressed. Here, we investigate the transcript levels and promoter methylation status of CYB5R2 in NPC derived cell lines and tumor biopsies and experimentally address its role as a tumor suppressor gene. We find that CYB5R2 transcript levels are decreased in NPC cell lines and tumor biopsies. Promoter hypermethylation of CYB5R2 was detected in all six tested NPC cell lines and in 84 % of primary NPC tumor biopsies but not in normal nasopharyngeal epithelium. Clinically, CYB5R2 methylation was associated with lymph node metastasis in NPC patients (P < 0.05). The endogenous expression of CYB5R2 could be restored in vitro by the methyltransferase inhibitor 5-aza-2′-deoxycytidine in NPC cell lines. Ectopic expression of CYB5R2 had an inhibitory effect on proliferation, clonogenicity and migration of NPC cells. Moreover, in vivo tests in nude mice indicated that ectopic expression of CYB5R2 reduces the tumorigenicity of CYB5R2-negative NPC cells. Collectively, these findings suggest that CYB5R2 may be a functional tumor suppressor gene, frequently inactivated by hypermethylation of its promoter in NPC. We report here the first instance of epigenetic downregulation in NPC tumor biopsies of a key enzyme, CYB5R2, which is responsible for the detoxification of environmental carcinogens. We propose the possibility of utilizing CYB5R2 promoter methylation as a diagnostic biomarker of NPC in the future.
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影响因子：
3.8
作者：
Turashvili, Gulisa;Bouchal, Jan;Baumforth, Karl;Wei, Wenbin;Dziechciarkova, Marta;Ehrmann, Jiri;Klein, Jiri;Fridman, Eduard;Skarda, Jozef;Srovnal, Josef;Hajduch, Marian;Murray, Paul;Kolar, Zdenek
通讯作者：
Kolar, Zdenek
影响因子：
6.4
作者：
Zhang, Zhe;Sun, Di;Huang, Guangwu
通讯作者：
Huang, Guangwu
影响因子：
14.9
作者：
Olek, A;Oswald, J;Walter, J
通讯作者：
Walter, J
影响因子：
2.8
作者：
Hecht, SS
通讯作者：
Hecht, SS
影响因子：
4.9
作者：
Vaughan, TL;Stewart, PA;Berwick, M
通讯作者：
Berwick, M