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去勢抵抗性前列腺癌關鍵enzalutamide耐藥相關基因的鑒定及RAD51功能的驗證

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發表時間：2024-08-28 14:12

2023年5月，安徽醫科大學上海臨床學院;安徽醫科大學第五臨床醫學院;同濟大學上海第十人民醫院檢驗科;安徽醫科大學上海臨床學院;安徽醫科大學第五臨床醫學院;上海交通大學醫學院上海兒童醫學中心檢驗科;上海市同濟第十人民醫院檢驗科;江蘇大學生命科學學院(Shanghai Clinical College,Anhui Medical University, No. 301, Yanchang Middle Road,Jingan District,Shanghai,200072, China;The Fifth School of Clinical Medicine,Anhui Medical University, Hefei, 230032, Anhui, China; Department of Clinical Laboratory, Shanghai Tenth People’sHospital of Tongji University, No.301, Yanchang Middle Road,Jingan District,200072, Shanghai,China；Shanghai Clinical College, Anhui Medical University, Shanghai, 200072, China；The Fifth School of Clinical Medicine, Anhui Medical University, Hefei, 230032, Anhui, China；Department of Clinical Laboratory Medicine, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127,China；Department of Clinical Laboratory, Shanghai Tenth People’s Hospital of Tongji；School of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu, 212013, China University, 200072, Shanghai, China) Wen Xu老師研究團隊在《Degruyter》上發表論文：

“Identification of key enzalutamide-resistance-related genes in castration-resistant prostate cancer and verification of RAD51 functions”

“去勢抵抗性前列腺癌關鍵enzalutamide耐藥相關基因的鑒定及RAD51功能的驗證”

Abstract：

Patients with castration-resistant prostate cancer (CRPC) often develop drug resistance after treatment with enzalutamide. The goal of our study was to identify the key genes related to enzalutamide resistance in CRPC and to provide new gene targets for future research on improving the efficacy of enzalutamide. Differential expression genes (DEGs) associated with enzalutamide were obtained from the GSE151083 and GSE150807 datasets. We used R software, the DAVID database, protein–protein interaction networks, the Cytoscape program, and Gene Set Cancer Analysis for data analysis. The effect of RAD51 knockdown on prostate cancer (PCa) cell lines was demonstrated using Cell Counting Kit-8, clone formation, and transwell migration experiments. Six hub genes with prognostic values were screened (RAD51, BLM, DTL, RFC2, APOE, and EXO1), which were significantly associated with immune cell infiltration in PCa. High RAD51, BLM, EXO1, and RFC2 expression was associated with androgen receptor signaling pathway activation. Except for APOE, high expression of hub genes showed a significant negative correlation with the IC50 of Navitoclax and NPK76-II-72-1. RAD51 knockdown inhibited the proliferation and migration of PC3 and DU145 cell lines and promoted apoptosis. Additionally, 22Rv1 cell proliferation was more significantly inhibited with RAD51 knockdown than without RAD51 knockdown under enzalutamide treatment. Overall, six key genes associated with enzalutamide resistance were screened (RAD51, BLM, DTL, RFC2, APOE, and EXO1), which are potential therapeutic targets for enzalutamide-resistant PCa in the future.

摘要：

去勢抵抗性前列腺癌(CRPC)患者常在恩雜魯胺治療后產生耐藥性。我們的研究目的是鑒定與CRPC中恩雜魯胺耐藥相關的關鍵基因，為今后提高恩雜魯胺療效的研究提供新的基因靶點。從GSE151083和GSE150807數據集中獲得與enzalutamide相關的差異表達基因(DEGs)。我們使用R軟件、DAVID數據庫、蛋白質-蛋白質相互作用網絡、Cytoscape程序和Gene Set Cancer Analysis進行數據分析。通過細胞計數試劑盒-8、克隆形成和transwell遷移實驗，證實了RAD51敲低對前列腺癌(PCa)細胞系的影響。篩選到6個具有預后價值的中樞基因(RAD51、BLM、DTL、RFC2、APOE和EXO1)，它們與前列腺癌免疫細胞浸潤有顯著相關性。RAD51、BLM、EXO1和RFC2的高表達與雄激素受體信號通路激活有關。除APOE外，hub基因的高表達與Navitoclax和NPK76-II-72-1的IC50呈顯著負相關。RAD51敲低抑制PC3和DU145細胞株的增殖和遷移，促進細胞凋亡。此外，在enzalutamide處理下，RAD51敲低比不敲低更明顯地抑制了22Rv1細胞的增殖。總的來說，我們篩選出了6個與enzalutamide耐藥相關的關鍵基因(RAD51、BLM、DTL、RFC2、APOE和EXO1)，它們是未來enzalutamide耐藥PCa的潛在治療靶點。