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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

位于单CpG二核苷酸的宫颈癌CXCL13基因启动子超甲基化促进细胞迁移

卷 20, 期 5, 2020

页: [355 - 363] 页: 9

弟呕挨: 10.2174/1568009620666200102123635

价格: $65

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摘要

背景: 趋化因子13 (CXCL13)及其趋化因子受体5 (CXCR5)参与各种癌症的发病。然而，它们在宫颈癌(CC)中的作用仍然未知。 目的: 讨趋化因子13 (CXCL13)及其受体在宫颈癌中的作用。 方法: 分析CXCL13/CXCR5及CXCR5+CD8+ T细胞在宫颈癌、宫颈上皮内瘤变(CIN)、正常宫颈上皮(NCE)组织及宫颈癌细胞系中的表达及浸润情况，并分析其临床意义。体外，我们利用CXCL13过表达和DNA甲基转移酶抑制(通过S110)研究其生物学功能和调控CXCL13表达的潜在机制。肿瘤生长和肝转移也评估在异种皮下种植模型。 结果: CXCR5+CD8+ T细胞浸润明显降低。CXCL13下调与FIGO分期、淋巴结转移、间质浸润深度、病理分级显著相关。CXCL13过表达抑制了CC细胞的迁移。CXCL13的下调与CC细胞系的高甲基化和原发性肿瘤活检相关。此外，CXCL13启动子元件中HIF-1a转录因子基序处的CpG二核苷酸在CC细胞中持续甲基化并与HIF-1a相关。在异种移植模型中，过表达CXCL13和S110显著抑制肿瘤生长和肝转移;而低表达则增加了CC患者的死亡风险。 结论: DNA甲基化依赖性CXCL13下调可能促进宫颈癌的发生和进展。

关键词: 宫颈癌

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