Department of Biological Sciences, Dong-A University, Busan 49315, Korea.
Department of Bioinformatics, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon 34113, Korea.
Int J Mol Sci. 2020 Nov 27;21(23):9025. doi: 10.3390/ijms21239025.
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.
DNA 修复缺陷是癌症发展的重要因素。高 DNA 修复活性会影响癌症的进展和化疗耐药性。抗癌药物引起的癌细胞中的 DNA 双链断裂可以通过非同源末端连接 (NHEJ) 和同源重组修复 (HRR) 来修复。我们之前的研究已经确定 E2F1 是膀胱癌进展的关键基因。在这项研究中，分析了与 E2F1 相关的 DNA 修复基因，并确定了参与 HRR 的 RAD54L。在膀胱癌患者的基因表达分析中，RAD54L 高表达的患者比 RAD54L 低表达的患者在癌症进展时的生存时间更短。本研究还表明，E2F1 直接结合 RAD54L 的启动子区域，并调节与 HRR 途径相关的 RAD54L 的转录。本研究还证实，在 MMC 处理的膀胱癌细胞中，E2F1 诱导的 RAD54L 修复了 DNA 断裂。总之，RAD54L 被确定为 E2F1 直接调控的新靶标。我们的研究结果表明，E2F1 和 RAD54L 可作为膀胱癌进展的诊断标志物，并代表潜在的治疗靶点。
