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High expression of RAD51 promotes DNA damage repair and survival in KRAS-mutant lung cancer cells

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收录情况： ◇ SCIE

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单位： [1]Department of pharmacy, First Affiliated Hospital of Nanchang University, Nanchang 330039, [2]Department of Oncology, Beijing Daxing District People’s Hospital, Capital Medical University, Beijing 102600, [3]Cancer center, Beijing Friendship Hospital, Capital Medical University, Beijing 10050, [4]Department of respiration, First Affiliated Hospital of Nanchang University, Nanchang 330039, China

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关键词： DNA damage repair KRAS Lung cancer MYC RAD51

摘要：

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.

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出版当年[2018]版：

大类 | 3 区生物

小类 | 3 区生化与分子生物学

最新[2025]版：

大类 | 4 区生物学

小类 | 4 区生化与分子生物学

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出版当年[2017]版：

Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

最新[2023]版：

Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

影响因子： 最新[2023版] 2.9 最新五年平均[2021-2025] 3.9 出版当年[2017版] 3.085 出版当年五年平均[2013-2017] 2.563 出版前一年[2016版] 3.089 出版后一年[2018版] 2.966

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第一作者单位： [1]Department of pharmacy, First Affiliated Hospital of Nanchang University, Nanchang 330039,

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