Research progress of deoxyribonucleic acid topoisomerase Ⅱ binding protein 1 and cancer
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摘要:
脱氧核糖核酸(DNA)损伤应答(DDR)是维持内稳态及肿瘤发展重要机制之一。DNA拓扑异构酶Ⅱβ结合蛋白1(TopBP1)在维持基因组稳定性及调控DDR相关信号通路中扮演着关键角色。最新研究发现, TopBP1通过多种分子机制促进肿瘤细胞的生长、转移及耐药，并且与肿瘤发病风险及预后显著相关。本文对TopBP1在乳腺及妇科、呼吸及消化系统肿瘤中的最新研究进展进行综述，以期深入了解TopBP1在不同肿瘤中的作用机制，推动其转化为临床标志物或药物干预靶点，并为基于DDR的抗癌策略提供新思路。
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关键词:
- 肿瘤 /
- DNA损伤应答 /
- DNA拓扑异构酶Ⅱβ结合蛋白1 /
- 信号通路 /
- 生物标记物
Abstract:Deoxyribonucleic acid (DNA) damage response (DDR) is one of crucial molecular mechanisms for homeostasis maintenance and tumor development. DNA topoisomerase Ⅱ binding protein 1 (TopBP1) plays a key role in maintaining genome stability and regulating DDR related signaling pathways. Recent studies have demonstrated TopBP1 promoted the growth, metastasis and drug resistance of cancer cells through various molecular mechanisms, and significantly correlated with cancer risk and clinical outcome. In this paper, the latest research progress of TopBP1 in breast and gynecological tumors, respiratory and digestive system tumors was reviewed, in order to further understand the mechanism of action of TopBP1 in different tumors, promote its transformation into clinical markers or drug intervention targets, and provide novel insights into the DDR based anti-cancer strategies.
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表 1 TopBP1在肿瘤中的生物学功能及临床意义
肿瘤类型 表达水平 抑癌/促癌 调控因子 生物学功能 临床意义 乳腺癌 — 促癌 CIP2A 增殖、调控G2-M位点 — 乳腺癌 — 促癌 MYB 增殖、调控细胞同源重组 — 乳腺癌 — 促癌 OTUD6A 增殖和转移 与放化疗抵抗相关 乳腺癌 — 促癌 PHF8 增殖 与预后、PARP抑制剂及铂类药物敏感性相关 乳腺癌 — 促癌 BRCA1/BRIP1 — 与PARP抑制剂敏感性相关 乳腺癌 — — — — 与乳腺癌早期诊断相关 卵巢癌 — — — — 与ATR抑制剂VE-821敏感性相关 宫颈癌 — 促癌 BRD4 参与调控细胞S期及有丝分裂 — 宫颈癌 — 促癌 病毒蛋白E2 参与HPV病毒生命周期 — 宫颈癌 上调 促癌 E2F1/p73 调控HPV病毒生命周期 — 肺癌 — 促癌 Treslin 增殖 — 非小细胞肺癌 — — — — 与总体生存相关 非小细胞肺癌 — — 突变P53 — 与阿霉素药物敏感性相关 脑转移性肺癌 上调 促癌 — — 与放射治疗效果相关 胰腺导管腺癌 — — GSK-3β — 与吉西他滨敏感性相关 胰腺癌 — — 恶性转化 判定吸烟相关胰腺癌的发病风险 胃癌 上调 — — — 与预后相关 胃癌 — 促癌 BRCC3 增殖和同源重组 — 胃癌 上调 — — 参与调控PARP1表达 与奥沙利铂耐药性相关 胃癌 — 促癌 锌指蛋白860 — 与术后复发相关 胃癌 — — Chk1 — 与人类表皮生长因子受体2 (Her-2)阳性胃癌的拉帕替尼治疗抵抗相关 结直肠癌 — — — — 与发病风险相关 结直肠癌 — 促癌 PLD1 调控肿瘤细胞凋亡 — 结直肠癌 — 促癌 — 侵袭和克隆形成 — 结直肠癌 — 促癌 CIP2A 增殖 — 前列腺癌 — 促癌 — 增殖和迁移 — 神经内分泌前列腺癌 促癌 — 增殖 — 鳞状细胞肿瘤 — — — 细胞分化 — 喉癌 — — — — 与淋巴结转移、病理分级及总体生存相关 骨肉瘤 上调 促癌 — — 与局部复发、肿瘤坏死率、阿霉素及顺铂的抵抗相关 
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