RAD51 Inhibition Shows Antitumor Activity in Hepatocellular Carcinoma

作者全名："Pan, Mingang; Sha, Yu; Qiu, Jianguo; Chen, Yunmeng; Liu, Lele; Luo, Muyu; Huang, Ailong; Xia, Jie"

作者地址："[Pan, Mingang; Sha, Yu; Chen, Yunmeng; Liu, Lele; Luo, Muyu; Huang, Ailong; Xia, Jie] Chongqing Med Univ, Key Lab Mol Biol Infect Dis, Minist Educ, Chongqing 400016, Peoples R China; [Sha, Yu] Henan Univ Chinese Med, Clin Med Inst 1, Zhengzhou 450000, Peoples R China; [Qiu, Jianguo] Chongqing Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Chongqing 400016, Peoples R China"

通信作者："Huang, AL; Xia, J (通讯作者)，Chongqing Med Univ, Key Lab Mol Biol Infect Dis, Minist Educ, Chongqing 400016, Peoples R China."

来源：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

ESI学科分类：CHEMISTRY

WOS号：WOS:000987345100001

JCR分区：Q2

影响因子：5.6

年份：2023

卷号：24

期号：9

开始页：　

结束页：　

文献类型：Article

关键词：RAD51; HCC; DNA damage; sorafenib; homologous recombination

摘要："Hepatocellular carcinoma (HCC), the major type of liver cancer, causes a high annual mortality worldwide. RAD51 is the critical recombinase responsible for homologous recombination (HR) repair in DNA damage. In this study, we identified that RAD51 was upregulated in HCC and that RAD51 silencing or inhibition reduced the proliferation, migration, and invasion of HCC cells and enhanced cell apoptosis and DNA damage. HCC cells with the combinatorial treatments of RAD51 siRNA or inhibitor and sorafenib demonstrated a synergistic effect in inhibiting HCC cell proliferation, migration, and invasion, as well as inducing cell apoptosis and DNA damage. Single RAD51 silencing or sorafenib reduced RAD51 protein expression and weakened HR efficiency, and their combination almost eliminated RAD51 protein expression and inhibited HR efficiency further. An in vivo tumor model confirmed the RAD51 inhibitor's antitumor activity and synergistic antitumor activity with sorafenib in HCC. RNA-Seq and gene set enrichment analysis (GSEA) in RAD51-inactivated Huh7 cells indicated that RAD51 knockdown upregulated cell apoptosis and G1/S DNA damage checkpoint pathways while downregulating mitotic spindle and homologous recombination pathways. Our findings suggest that RAD51 inhibition exhibits antitumor activities in HCC and synergizes with sorafenib. Targeting RAD51 may provide a novel therapeutic approach in HCC."

基金机构：Science and Technology Research Program of Chongqing Education Commission [KJQN202100424]; Natural Science Foundation Project of Chongqing [cstc2018jcyjAX0825]

基金资助正文：The study was supported by grants from the Science and Technology Research Program of Chongqing Education Commission (no. KJQN202100424) and the Natural Science Foundation Project of Chongqing (no. cstc2018jcyjAX0825).