Objective To investigate the impacts of miR-224 on biochemical recurrence and angiogenesis of prostate cancer. Methods Bioinformatics analysis and luciferase reporter assay were performed to predict the gene that can be directly inhibited by miR-224. Taylor database was used for confirming the expressions of CNNM1 and miR-224, and their correlations with biochemical recurrence of prostate cancer. Finally, the impacts of CNNM1 and miR-224 on angiogenesis of prostate cancer were explored by PC3 cell in vitro and in vivo. Results CNNM1 was directly regulated by miR-224, and their expression levels were negatively correlated in prostate cancer tissue ( r=-0.378, P<0.05). miR-224 was negatively correlated to, while CNNM1 was positively correlated to biochemical recurrence of prostate cancer (P<0.05). The expressions of CNNM1 and CD31 decreased in the PC3 cells overexpressing miR-224 (P<0.05). However, CNNM1 enhanced the expression level of CD31 (P<0.05). The immunochemical staining of the transplantation tumor in the nude mice displayed that miR-224 overexpression could suppress angiogenesis in the prostate cancer tissue. Conclusions miR-224 suppresses angiogenesis and biochemical recurrence of prostate cancer by targeting CNNM1.%目的 研究microRNA-224(miR-224)对前列腺癌生化复发及血管生成的影响.方法 生物信息学分析及荧光素酶报告实验预测细胞周期调节蛋白1(CNNM1)受miR-224负性调控.Taylor前列腺癌数据库分析、验证CNNM1、miR-224的表达关系及其与前列腺癌生化复发的相关性.前列腺癌PC3细胞体外培养及动物体内成瘤实验研究CNNM1、miR-224表达对前列腺癌微血管生成标志物CD31的影响.结果 CNNM1表达受miR-224靶向调节,前列腺癌组织中CNNM1与miR-224的表达呈负相关(P<0.05).miR-224与前列腺癌的生化复发呈负相关(P<0.05),CNNM1与前列腺的生化复发呈正相关(P<0.05);在过表达miR-224的PC3细胞株内,CNNM1和CD31的表达量下降;CNNM1过表达能促进CD31的生成.前列腺癌细胞裸鼠体内成瘤组织免疫组织化学法染色提示,miR-224过表达能抑制前列腺癌组织内微血管形成.结论 miR-224通过靶向调控CNNM1表达,抑制前列腺癌微血管形成,控制前列腺癌生化复发.
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