长链非编码PCA3靶向miR-194影响前列腺癌细胞增殖和凋亡行为  

Effects of long-chain non-coding PCA3 targeting miR-194 expression on proliferation and apoptosis of prostate cancer cells

作　　者：韩兴涛[1] 杨凌博 魏澎涛[1] 李小辉 孙建涛[1] 杨锦建[2] HAN Xing-Tao;Yang Ling-Bo;WEI Peng-Tao;LI Xiao-Hui;SUN Jian-Tao;YANG Jin-Jian(Department of Urology,Luoyang Central Hospital,Luoyang 471000,China)

机构地区：[1]洛阳市中心医院泌尿外科,洛阳471000 [2]郑州大学第一附属医院泌尿外科,郑州450052

出　　处：《中国免疫学杂志》2018年第12期1766-1770,1775,共6页Chinese Journal of Immunology

基　　金：国家自然科学基金(81570685)

摘　　要：目的:探讨长链非编码PCA3靶向miR-194的表达通过ERK信号通路对前列腺癌细胞增殖和凋亡的作用及机制。方法:q PCR检测PCA3和miR-194在不同前列腺癌细胞中的表达情况;双荧光素酶报告基因检测PCA3与miR-194的相互作用;克隆形成实验和凋亡实验检测抑制PCA3后前列腺细胞增殖能力和凋亡行为的变化,及过表达miR-194后前列腺细胞增殖能力和凋亡行为的变化;Western blot检测抑制PCA3后ERK信号通路蛋白的表达水平及过表达miR-194后ERK信号通路蛋白的表达水平变化。裸鼠体内成瘤试验检测PCA3对前列腺癌细胞成瘤能力的影响。结果:与其他前列腺癌细胞相比,LNCa P细胞中PCA3的表达水平最高,miR-194的表达水平较低;双荧光素酶试验证实PCA3可以调控miR-194的表达及活性,抑制PCA3的表达可以减弱前列腺癌细胞的增殖能力,加强其凋亡行为;过表达miR-194后前列腺癌细胞的增殖能力和凋亡行为得到一定的恢复;抑制PCA3的表达可以下调ERK信号通路的蛋白表达,抑制ERK信号通路的激活;同时过表达miR-194后可以逆转PCA3对ERK信号通路的抑制作用。抑制PCA3的表达后可以有效减弱前列腺癌细胞的体内成瘤能力。结论:PCA3可以靶向调节miR-194通过ERK信号通路调控前列腺癌细胞的增殖和凋亡行为。Objective:To investigate the effect and mechanism of long-chain non-coding PCA3targeting miR-194expression on proliferation and apoptosis of prostate cancer cells through ERK signaling pathway.Methods:The expression of PCA3and miR-194in different prostate cancer cells was detected by qPCR.Double luciferase reporter gene was used to detect the interaction between PCA3and miR-194.Clonal assay and apoptotic test were used to inhibit the proliferation and apoptosis of prostate cells after overexpression of miR-194.Western blot was used to detect the expression of ERK signal pathway protein after PCA3and the expression of ERK signal pathway protein after overexpression of miR-194.The effect of PCA3on tumorigenesis of prostate cancer cells was detected by tumor formation in nude mice.Results:Compared with other prostate cancer cells,the expression level of PCA3was the highest in LNCaP cells and the expression level of miR-194was lower.Double-luciferase assay confirmed that PCA3can regulate the expression and activity of miR-194,inhibition of PCA3expression can attenuate the proliferation of prostate cancer cells and enhance the apoptotic behavior.Overexpression of miR-194could enhances the proliferation of prostate cancer cells.Inhibition of PCA3expression could down-regulate the expression of ERK signaling pathway and inhibit the activation of ERK signaling pathway.At the same time,overexpression of miR-194could reverse the inhibitory effect of PCA3on ERK signaling pathway.Inhibition of PCA3expression could effectively weaken the prostate cancer cells in vivo tumorigenic ability.Conclusion:PCA3can regulate the proliferation and apoptosis of prostate cancer cells through the regulation of miR-194through ERK signaling pathway.

关 键 词：PCA3 前列腺癌 miR-194 ERK 

分 类 号：R737.25[医药卫生—肿瘤]