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目的 探讨前列腺癌中同源盒基因D10(HOXD10)与类固醇5α还原酶1(SRD5A1)的关系及其对SRD5A1的调控作用.方法 通过Taylor和肿瘤基因组图谱(TCGA)数据库分析HOXD10与SRD5A1在前列腺癌的表达及两者的关系;构建HOXD10过表达前列腺癌细胞LNCaP,利用实时定量反转录聚合酶链反应(RT-qPCR)和蛋白质印迹法(Western blot)检测HOXD10对SRD5A1的影响;使用免疫组织化学方法分析HOXD10和SRD5A1在人前列腺癌组织的关系,应用GraphPad Prism Version 6软件进行统计分析.结果 随着前列腺癌的疾病进展,HOXD10的mRNA表达水平逐渐降低(Taylor:良性组织:8.94±0.09,原发灶:7.93±0.05,转移灶:7.66±0.11,F=43.72,P＜0.05),而SRD5A1则逐渐升高(Taylor:良性组织:7.75 ±0.02,原发灶:7.79±0.02,转移灶:7.98±0.01,F=5.306,P＜ 0.05),两者呈显著负相关(TCGA:HOXD10:80.72±1.60,SRD5A1:231.60±2.48;r=-0.220,P＜0.01);且HOXD10过表达的前列腺癌细胞中SRD5A1的表达显著减少(x2 =5.868,P＜0.05)(RT-qPCR:LNCaP-HOXD10过表达组SRD5A1:0.66±0.02,LNCaP-空载组SRD5A1:0.99±0.00,t=12.12,P＜0.01;Western blot:LNCaP-HOXD10过表达组SRD5A1:0.58±0.00,LNCaP-空载组SRD5A1:0.82±0.02,t=12.12,P＜0.01).结论 HOXD10在前列腺癌中负性调控SRD5A1.

Objective To investigate the relationship between homeobox gene D10 (HOXD10)and steroid 5-alpha reductase 1 (SRD5A1) and the effect of the former on the latter in prostate cancer cells.Methods Expression of HOXD10 and SRD5A1 and their correlation was analyzed basing on Taylor and TCGA database.Then HOXD10-overexpressing prostate cancer LNCaP cells was constructed,and the effect of HOXD10 on SRD5A1 was detected by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) and Western blotting.Immunohistochemistry was used to analyze the expression of HOXD10 and SRD5A1 in human prostate cancer tissues.Statisticalanalysis of data using the GraphPad Prism Version 6 software.Results mRNA expression of HOXD10 decreased gradually with the progression of prostate cancer (Taylor:Benign:8.94 ± 0.09,Primary:7.93 ± 0.05,Met:7.66 ± 0.11,F =43.72,P ＜ 0.05),while SRD5A1 increased gradually (Taylor:Benign:7.75 ± 0.02,Primary:7.79 ± 0.02,Met:7.98 ± 0.01,F =5.306,P ＜ 0.05),and demonstrated a significant negative correlation (TCGA:HOXD10:80.72 ± 1.60,SRD5A1:231.60 ± 2.48;r =-0.220,P ＜ 0.01).Moreover,the expression of SRD5A1 in prostate cancer cells or patients was significantly reduced in which with higher expression of HOXD10 (Immunohistochemistry:x2 =5.868,P ＜ 0.05).(RT-qPCR:overexpressing HOXD10-LNCaP SRD5A1:0.66 ±0.02,vector-LNCaP SRD5A1:0.99 ±0.00,t =11.31,P ＜0.01;Western blotting:overexpressing HOXD10-LNCaP SRD5A1:0.58 ± 0.00,vector-LNCaP SRD5A1:0.82 ± 0.02,t =11.31,P ＜ 0.01).Conclusion HOXD10 negatively regulates SRD5A1 in prostate cancer and may provide a new strategy for endocrine therapy of prostate cancer.