MicroRNA-224靶向CNNM1抑制前列腺癌血管生成的实验研究

miR-224 inhibits angiogenesis of prostate cancer by targeting cyclin protein M1

摘要:

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 与前列腺癌的生发复发呈负相关（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。

Abstract:

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 and . 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.