BMB Reports 2019; 52(2): 151-156  https://doi.org/10.5483/BMBRep.2019.52.2.213
High expression of RAD51 promotes DNA damage repair and survival in KRAS-mutant lung cancer cells
Jinfang Hu1, Zhiguo Zhang2, Lei Zhao3, Li Li3, Wei Zuo4,* and Lei Han2,*
1Department of pharmacy, First Affiliated Hospital of Nanchang University, Nanchang 330039, 2Department of Oncology, Beijing Daxing District People’s Hospital, Capital Medical University, Beijing 102600, 3Cancer center, Beijing Friendship Hospital, Capital Medical University, Beijing 10050, 4Department of respiration, First Affiliated Hospital of Nanchang University, Nanchang 330039, China
Correspondence to: Wei Zuo, Tel: +86-18170025400; Fax: +86-791-88699340; E-mail: zuowei888@tom.com; Lei Han, Tel: +86-13482881659; Fax: +86-10-69208013; E-mail: leihan1029@gmail.com
Received: September 14, 2018; Revised: October 9, 2018; Accepted: November 12, 2018; Published online: February 28, 2019.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

cc This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
RAD51 recombinase plays a critical role in homologous recombination and DNA damage repair. Here we showed that expression of RAD51 is frequently upregulated in lung cancer tumors compared with normal tissues and is associated with poor survival (hazard ratio (HR) = 2, P = 0.0009). Systematic investigation of lung cancer cell lines revealed higher expression of RAD51 in KRAS mutant (MT) cells compared to wildtype (WT) cells. We further showed that MT KRAS, but not WT KRAS, played a critical role in RAD51 overexpression via MYC. Moreover, our results revealed that KRAS MT cells are highly dependent on RAD51 for survival and depletion of RAD51 resulted in enhanced DNA double strand breaks, defective colony formation and cell death. Together, our results suggest that mutant KRAS promotes RAD51 expression to enhance DNA damage repair and lung cancer cell survival, suggesting that RAD51 may be an effective therapeutic target to overcome chemo/radioresistance in KRAS mutant cancers.
Keywords: DNA damage repair, KRAS, Lung cancer, MYC, RAD51


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