泛素蛋白酶系统对前列腺癌 DNA 损伤反应的影响(综述)。

IF 2.4 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Experimental and therapeutic medicine Pub Date : 2023-11-24 DOI:10.3892/etm.2023.12321
Yan Lin, Xiaofeng Jin
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引用次数: 0

摘要

基因组不稳定性是癌症的一个基本特征,细胞DNA损伤应答(DDR)缺陷通过破坏基因组稳定性来驱动肿瘤发生。多项研究发现了 DDR 相关基因的异常,而泛素-蛋白酶体系统(UPS)功能失调是转移性去势抵抗性前列腺癌(PCa)中最常见的分子事件。例如,Speckle 型 BTB/POZ 蛋白-Ser119 的突变导致 DDR 下游靶点激活缺陷。Skp2 过度上调会抑制同源重组修复,促进细胞生长和迁移。去泛素化酶--泛素特异性蛋白酶12的异常高表达稳定了E3连接酶MDM2,进一步导致p53降解,造成DDR中断和基因组不稳定。本综述介绍了DDR的基本途径、UPS功能障碍及其诱导的由基因组不稳定性介导的DDR改变,特别是UPS和DDR改变作为生物标志物和治疗靶点在PCa治疗中的潜在应用。
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Effect of ubiquitin protease system on DNA damage response in prostate cancer (Review).
Genomic instability is an essential hallmark of cancer, and cellular DNA damage response (DDR) defects drive tumorigenesis by disrupting genomic stability. Several studies have identified abnormalities in DDR-associated genes, and a dysfunctional ubiquitin-proteasome system (UPS) is the most common molecular event in metastatic castration-resistant prostate cancer (PCa). For example, mutations in Speckle-type BTB/POZ protein-Ser119 result in DDR downstream target activation deficiency. Skp2 excessive upregulation inhibits homologous recombination repair and promotes cell growth and migration. Abnormally high expression of a deubiquitination enzyme, ubiquitin-specific protease 12, stabilizes E3 ligase MDM2, which further leads to p53 degradation, causing DDR interruption and genomic instability. In the present review, the basic pathways of DDR, UPS dysfunction, and its induced DDR alterations mediated by genomic instability, and especially the potential application of UPS and DDR alterations as biomarkers and therapeutic targets in PCa treatment, were described.
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来源期刊
Experimental and therapeutic medicine
Experimental and therapeutic medicine MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
1.50
自引率
0.00%
发文量
570
审稿时长
1 months
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