miR-654-5p通过抑制FASN介导的脂肪酸合成增强前列腺癌细胞对多西他赛的敏感性  

Effects of miR-654-5p on increasing the sensitivity of prostate cancer cells to docetaxel by inhibiting FASN-mediated fatty acid synthesis

作　　者：林菲 黄旭云 陈佳茵 柯志滨 陈烨辉 林云知 郑清水[1] 魏勇[1] 薛学义[1] 许宁[1] LIN Fei;HUANG Xuyun;CHEN Jiayin;KE Zhibin;CHEN Yehui;LIN Yunzhi;ZHENG Qingshui;WEI Yong;XUE Xueyi;XU Ning(Department of Urology,First Affiliated Hospital,Fujian Medical University,Fuzhou 350005,China)

机构地区：[1]福建医科大学附属第一医院泌尿外科,福州350005

出　　处：《现代泌尿生殖肿瘤杂志》2025年第2期111-118,共8页Journal of Contemporary Urologic and Reproductive Oncology

摘　　要：目的探究mi R-654-5p对前列腺癌细胞多西他赛敏感性和增殖能力的影响及其机制。方法实时荧光定量PCR(RT-q PCR)检测前列腺上皮细胞和前列腺癌细胞中mi R-654-5p表达情况。将mi R-654-5p mimics及mi R-654-5p inhibitor分别转染前列腺癌细胞系PC-3和DU145细胞,采用CCK8检测细胞增殖并计算多西他赛半抑制浓度(IC50)。酶联免疫吸附实验(ELISA)检测敲减或过表达mi R-654-5p后前列腺癌细胞中游离脂肪酸含量。生物信息学预测mi R-654-5p靶基因,并通过RT-q PCR、Western Blot、双萤光素酶报告基因实验及功能回复验证。结果miR-654-5p在前列腺癌细胞系PC-3和DU145中表达显著降低(P<0.05)。转染mi R-654-5p inhibitor后,PC-3和DU145细胞增殖能力显著增强,细胞内游离脂肪酸含量显著增加,对多西他赛敏感性显著降低(P<0.05)。脂肪酸合成酶FASN是mi R-654-5p的靶基因。脂质合成抑制剂Cerulenin可逆转mi R-654-5p下调对前列腺癌细胞增殖和多西他赛化疗耐药的促进作用。结论miR-654-5p可通过抑制脂肪酸合成代谢、抑制前列腺癌细胞增殖并增强多西他赛化疗敏感性。Objective To explore the effects and mechanisms of miR-654-5p on proliferation and docetaxel sensitivity of prostate cancer cells.Methods The expression levels of miR-654-5p in prostatic epithelial cell line and prostate cancer cell lines were detected by RT-qPCR.Next,miR-654-5p mimics and miR-654-5p inhibitor were transfected into PC-3 and DU145 cells,respectively.Cell proliferation was detected by the Cell-Counting kit 8(cck-8)assay and the IC50 of docetaxel was calcaulated.ELISA assay was performed to detect the levels of free fatty acids in prostate cancer cells with either silenced or overexpressed miR-654-5p.Bioinformatics methods were used to predict and analyze the target gene of miR-654-5p.The results were further verified by RT-qPCR,Western Blot,dual-luciferase reporter assay and rescue experiment.Results The expression of miR-654-5p was significantly lower in prostate cancer cell lines(PC-3 and DU145)compared to the prostatic epithelial cell line(RWPE-1)(P<0.05).After transfection with miR-654-5p inhibitor,the cell proliferation and the content of free fatty acids increased significantly(P<0.05).In addition,transfection with miR-654-5p inhibitor in PC-3 and DU145 cells decreased the sensitivity to docetaxel(P<0.05).Fatty acid synthase(FASN)was the target gene of miR-654-5p.The lipid synthesis inhibitor Cerulenin could reverse the promoting effect of miR-654-5p downregulation on cell proliferation and docetaxel chemotherapy resistance in prostate cancer.Conclusions MiR-654-5p could suppress the cell proliferation and increase the sensitivity to docetaxel chemotherapy by inhibiting FASN-mediated fatty acid synthesis in prostate cancer cells.

关 键 词：前列腺癌 miR-654-5p 多西他赛 化疗敏感性 脂肪酸合成 

分 类 号：R737.25[医药卫生—肿瘤]