Investigation of EZH2 pathways for novel epigenetic treatment strategies in oropharyngeal cancer.
Investigation of EZH2 pathways for novel epigenetic treatment strategies in oropharyngeal cancer.
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DOI：
10.1186/s40463-016-0168-9
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发表时间：
2016-10-28
期刊：
影响因子：
--
通讯作者：
Biron VL
中科院分区：
文献类型：
--
作者：
Idris S;Lindsay C;Kostiuk M;Andrews C;Côté DW;O'Connell DA;Harris J;Seikaly H;Biron VL
近几十年来，由于口咽部致癌性人乳头状瘤病毒(HPV)感染的增加，口咽鳞状细胞癌(OPSCC)的发病率在全球范围内呈上升趋势。EZH2是一种表观遗传调节蛋白，与几种人类癌症的肿瘤侵袭性和负生存结果相关。我们的目标是确定EZH2在HPV阳性和阴性OPSCC中作为潜在的治疗表观遗传学靶点的作用。用免疫组织化学(IHC)和滴状数字聚合酶链式反应(DdPCR)检测2株HPV阳性和2株HPV阴性细胞株中EZH2的表达。然后培养细胞，并用3种EZH2表观遗传抑制剂之一(3-去氮杂环素A、GSK-343和EPZ005687)或DMSO(对照组)处理。治疗2、4、7天后，通过基因表达、细胞存活和增殖实验对细胞进行分析和比较。与HPV阴性细胞系相比，EZH2靶向对HPV阳性细胞系的生长和存活的抑制作用更大。根据Ki67、CCND1、Met和PTEN/PIK3CA的HPV阳性不同，OPSCC中重要基因的表达谱也不同，但EGFR、CDKN2A和P53的表达谱没有变化。抑制EZH2对培养的OPSCC细胞具有抗肿瘤作用，这种作用在HPV阳性细胞系中更为明显。EZH2是治疗OPSCC的一个有前景的表观遗传学靶点。
In recent decades, the incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been rising worldwide as a result of increasing oncogenic human papillomavirus (HPV) infections in the oropharynx. EZH2 is an epigenetic regulatory protein associated with tumor aggressiveness and negative survival outcomes in several human cancers. We aimed to determine the role of EZH2 as a potential therapeutic epigenetic target in HPV-positive and negative OPSCC. The expression of EZH2 was measured by immunohistochemistry (IHC) and droplet digital PCR (ddPCR) in 2 HPV-positive and 2 HPV-negative cell lines. The cell lines were then cultured and treated with one of 3 EZH2 epigenetic inhibitors (3-deazaneplanocin A, GSK-343 and EPZ005687) or DMSO (control). Following 2, 4 and 7 days of treatment, cells were analyzed and compared by gene expression, cell survival and proliferation assays. EZH2 targeting resulted in greater inhibition of growth and survival in HPV-positive compared to HPV-negative cells lines. The expression profile of genes important in OPSCC also differed according to HPV-positivity for Ki67, CCND1, MET and PTEN/PIK3CA, but remained unchanged for EGFR, CDKN2A and p53. Inhibition of EZH2 has anti-tumorigenic effects on OPSCC cells in culture that is more pronounced in HPV-positive cell lines. EZH2 is a promising epigenetic target for the treatment of OPSCC.
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影响因子：
--
作者：
Li Z;Wang Y;Qiu J;Li Q;Yuan C;Zhang W;Wang D;Ye J;Jiang H;Yang J;Cheng J
通讯作者：
Cheng J
DOI：
10.1186/s40463-015-0062-x
发表时间：
2015-02-24
期刊：
Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale
影响因子：
--
作者：
Cooper T;Biron VL;Fast D;Tam R;Carey T;Shmulevitz M;Seikaly H
通讯作者：
Seikaly H
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影响因子：
6.2
作者：
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通讯作者：
Chen, Wantao
影响因子：
3.4
作者：
Clark, Jessica;Jeffery, Caroline C.;Biron, Vincent L.
通讯作者：
Biron, Vincent L.
DOI：
10.1111/1440-1681.12382
发表时间：
2015-05-01
影响因子：
2.9
作者：
Ding, Muyang;Zhang, Hang;Gao, Yane
通讯作者：
Gao, Yane