E2F1 Promotes Progression of Bladder Cancer by Modulating RAD54L Involved in Homologous Recombination Repair

• Published in: International journal of molecular sciences Vol. 21; no. 23; p. 9025
• Main Authors: Mun, Jeong-Yeon, Baek, Seung-Woo, Park, Won Young, Kim, Won-Tae, Kim, Seon-Kyu, Roh, Yun-Gil, Jeong, Mi-So, Yang, Gi-Eun, Lee, Jong-Ho, Chung, Jin Woong, Choi, Yung Hyun, Chu, In-Sun, Leem, Sun-Hee
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27-11-2020; MDPI
• Subjects: Apoptosis; Base Sequence; Binding sites; Bladder cancer; Cancer; Cancer therapies; Cell cycle; Cell Line, Tumor; Chemoresistance; Cluster analysis; Deoxyribonucleic acid; Diagnostic systems; Disease Progression; DNA; DNA Breaks, Double-Stranded - drug effects; DNA damage; DNA Helicases - metabolism; DNA repair; DNA-Binding Proteins - metabolism; E2F1; E2F1 Transcription Factor - metabolism; Gene amplification; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Homologous recombination; Homologous recombination repair; Homology; Humans; Medical prognosis; Mitomycin - pharmacology; Non-homologous end joining; Prognosis; prognostic biomarkers; RAD54L; Recombinational DNA Repair - genetics; Repair; Transcription; Transcription factors; Transcriptional Activation - genetics; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - pathology; E2F1; prognostic biomarkers; RAD54L; bladder cancer; homologous recombination repair
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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.