Rad54l-KO Mouse

Rad54L, a member of the SWI2/SNF2 protein family, is a DNA motor protein with multiple roles in homologous recombination DNA repair (HR), especially in the repair of DNA double-strand breaks (DSBs) [2,4,5,7]. The HR pathway in which it is involved has been linked to tumorigenesis, drug resistance, and DNA replication dynamics [1,2,3,4,6,7].

In cancer research, high Rad54L expression in bladder cancer tissues is associated with poor prognosis, promoting abnormal cell proliferation by regulating the cell cycle and senescence, and may be associated with p53, p21, and pRB [1]. In hepatocellular carcinoma, its up-regulation in the HRR pathway is positively correlated with tumor pathological staging and negatively with patient overall survival, and is associated with the Edmondson-Steiner grade and the proliferation-related gene Ki67 [3]. In early-stage lung adenocarcinoma, high Rad54L expression is related to worse overall survival, and it is an independent prognostic factor [6]. In pan-cancer analysis, Rad54L is highly expressed in most tumors, promotes HCC cell proliferation and migration, and is correlated with immune cell infiltration, tumor mutation burden, and immune checkpoints [7]. In replication fork reversal, Rad54L restrains fork progression, functions as a fork remodeler, and has different requirements in two RAD51-mediated fork reversal pathways [2,4].

In conclusion, Rad54L is crucial in homologous recombination DNA repair and has significant implications in cancer development and progression, as revealed by various in vivo-like studies on cancer tissues. Understanding Rad54L can provide insights into tumorigenesis mechanisms and potential therapeutic targets for cancers such as bladder, liver, and lung cancers.

References:

1. Wang, Yinzhao, Zhou, Tailai, Chen, Hengxing, Dao, Pinghong, Chen, Minfeng. 2022. Rad54L promotes bladder cancer progression by regulating cell cycle and cell senescence. In Medical oncology (Northwood, London, England), 39, 185. doi:10.1007/s12032-022-01751-7. https://pubmed.ncbi.nlm.nih.gov/36071250/

2. Uhrig, Mollie E, Sharma, Neelam, Maxwell, Petey, Mazin, Alexander V, Wiese, Claudia. . Disparate requirements for RAD54L in replication fork reversal. In Nucleic acids research, 52, 12390-12404. doi:10.1093/nar/gkae828. https://pubmed.ncbi.nlm.nih.gov/39315725/

3. Li, Hongda, Zhuang, Haiwen, Gu, Tengfei, Xu, Sanrong, Zhou, Qing. 2023. RAD54L promotes progression of hepatocellular carcinoma via the homologous recombination repair pathway. In Functional & integrative genomics, 23, 128. doi:10.1007/s10142-023-01060-w. https://pubmed.ncbi.nlm.nih.gov/37071224/

4. Uhrig, Mollie E, Sharma, Neelam, Maxwell, Petey, Mazin, Alexander V, Wiese, Claudia. 2024. Disparate requirements for RAD54L in replication fork reversal. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.07.26.550704. https://pubmed.ncbi.nlm.nih.gov/37546955/

5. Selemenakis, Platon, Sharma, Neelam, Uhrig, Mollie E, Sung, Patrick, Wiese, Claudia. 2022. RAD51AP1 and RAD54L Can Underpin Two Distinct RAD51-Dependent Routes of DNA Damage Repair via Homologous Recombination. In Frontiers in cell and developmental biology, 10, 866601. doi:10.3389/fcell.2022.866601. https://pubmed.ncbi.nlm.nih.gov/35652094/

6. Zheng, Shaopeng, Yao, Lintong, Li, Fasheng, Lanuti, Michael, Zhou, Haiyu. 2021. Homologous recombination repair rathway and RAD54L in early-stage lung adenocarcinoma. In PeerJ, 9, e10680. doi:10.7717/peerj.10680. https://pubmed.ncbi.nlm.nih.gov/33628633/

7. Zhou, Yongzhen, Qiu, Chenjie, Fu, Qingsheng, Qin, Xihu, Wu, Baoqiang. 2023. Pan-Cancer Analysis of Oncogenic Role of RAD54L and Experimental Validation in Hepatocellular Carcinoma. In Journal of inflammation research, 16, 3997-4017. doi:10.2147/JIR.S426558. https://pubmed.ncbi.nlm.nih.gov/37719938/