E2F1 Promotes Progression of Bladder Cancer by Modulating RAD54L Involved in Homologous Recombination Repair.
E2F1 Promotes Progression of Bladder Cancer by Modulating RAD54L Involved in Homologous Recombination Repair.
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E2F1通过调节参与原位修复的RAD54 L促进膀胱癌进展
DOI：
10.3390/ijms21239025
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发表时间：
2020-11-27
影响因子：
5.6
通讯作者：
Leem SH
中科院分区：
文献类型：
--
作者：
Mun JY;Baek SW;Park WY;Kim WT;Kim SK;Roh YG;Jeong MS;Yang GE;Lee JH;Chung JW;Choi YH;Chu IS;Leem SH
DNA修复缺陷是癌症发生的重要因素。高DNA修复活性可影响癌症进展和化疗耐药。抗癌药物引起的肿瘤细胞DNA双链断裂可通过非同源末端连接（NHEJ）和同源重组修复（HRR）修复。我们之前的研究已经确定E2F1是膀胱癌进展的关键基因。本研究分析了与E2F1相关的DNA修复基因，鉴定出参与HRR的RAD54L。在膀胱癌患者的基因表达分析中，RAD54L高表达患者的生存期比RAD54L低表达患者的生存期更短。本研究还发现E2F1直接结合RAD54L的启动子区域，调控与HRR通路相关的RAD54L的转录。本研究也证实了在MMC处理的膀胱癌细胞中，E2F1诱导的RAD54L能够修复DNA断裂。综上所述，RAD54L被确定为E2F1直接调控的新靶点。我们的研究结果表明，E2F1和RAD54L可以作为膀胱癌进展的诊断标志物，并代表潜在的治疗靶点。
DNA repair defects are important factors in cancer development. High DNA repair activity can affect cancer progression and chemoresistance. DNA double-strand breaks in cancer cells caused by anticancer agents can be restored by non-homologous end joining (NHEJ) and homologous recombination repair (HRR). Our previous study has identified E2F1 as a key gene in bladder cancer progression. In this study, DNA repair genes related to E2F1 were analyzed, and RAD54L involved in HRR was identified. In gene expression analysis of bladder cancer patients, the survival of patients with high RAD54L expression was shorter with cancer progression than in patients with low RAD54L expression. This study also revealed that E2F1 directly binds to the promoter region of RAD54L and regulates the transcription of RAD54L related to the HRR pathway. This study also confirmed that DNA breaks are repaired by RAD54L induced by E2F1 in bladder cancer cells treated with MMC. In summary, RAD54L was identified as a new target directly regulated by E2F1. Our results suggest that, E2F1 and RAD54L could be used as diagnostic markers for bladder cancer progression and represent potential therapeutic targets.
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DOI：
10.4161/cc.7.18.6679
发表时间：
2008-09-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Mao Z;Bozzella M;Seluanov A;Gorbunova V
通讯作者：
Gorbunova V
影响因子：
10.5
作者：
Ferreira, MG;Cooper, JP
通讯作者：
Cooper, JP
DOI：
10.1016/j.mrfmmm.2014.08.007
发表时间：
2015-06-01
影响因子：
2.3
作者：
Dupuy, Aurelie;Sarasin, Alain
通讯作者：
Sarasin, Alain
DOI：
10.1038/nrc3088
发表时间：
2011-06-24
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
8
作者：
Berton, TR;Mitchell, DL;Johnson, DG
通讯作者：
Johnson, DG