抑制 miR-423-5p 通过靶向 GRIM-19 抑制前列腺癌。

Inhibition of miR-423-5p suppressed prostate cancer through targeting GRIM-19.

机构信息

Department of Urology, Zhangzhou Hospital Affiliated to Fujian Medical University, Zhangzhou 363000, Fujian, China.

出版信息

Gene. 2019 Mar 10;688:93-97. doi: 10.1016/j.gene.2018.11.021. Epub 2018 Nov 8.

DOI:10.1016/j.gene.2018.11.021

PMID:30415005

Abstract

OBJECTIVE

To determine the effect of miR-423-5p on the progression of prostate cancer (PC).

METHODS

miR-423-5p and GRIM-19 expressions were detected by qRT-PCR and western blot. PC cell proliferation was measured by MTT assay. PC cell apoptosis was detected by flow cytometry. Dual luciferase reporter assay was used to confirm the interaction between miR-423-5p and GRIM-19.

RESULTS

Compared with normal prostate tissues and prostate epithelial cell HPrEC, miR-423-5p was up-regulated in human PC tissues and PC3 cells, whereas GRIM-19 expression was decreased. Inhibition of miR-423-5p suppressed PC3 cell proliferation, promoted PC3 cell apoptosis, and decreased anti-apoptosis protein BCL-2 expression. GRIM-19 was a target of miR-423-5p, and GRIM-19 was negatively regulated by miR-423-5p in PC3 cells. In addition, miR-423-5p knockdown inhibited the proliferation and promoted the apoptosis of PC3 cells through GRIM-19. In vivo experiments showed that miR-423-5p inhibitor administration reduced tumor volume, down-regulated miR-423-5p and GRIM-19 expressions in PC tissues of nude mice.

CONCLUSION

Inhibition of miR-423-5p suppressed PC through targeting GRIM-19.

摘要

目的

探讨 miR-423-5p 对前列腺癌（PC）进展的影响。

方法

采用 qRT-PCR 和 Western blot 检测 miR-423-5p 和 GRIM-19 的表达。MTT 法检测 PC 细胞增殖。流式细胞术检测 PC 细胞凋亡。双荧光素酶报告基因实验验证 miR-423-5p 与 GRIM-19 的相互作用。

结果

与正常前列腺组织和前列腺上皮细胞 HPrEC 相比，miR-423-5p 在人 PC 组织和 PC3 细胞中上调，而 GRIM-19 表达下调。抑制 miR-423-5p 抑制 PC3 细胞增殖，促进 PC3 细胞凋亡，降低抗凋亡蛋白 BCL-2 的表达。GRIM-19 是 miR-423-5p 的靶基因，miR-423-5p 在 PC3 细胞中负调控 GRIM-19。此外，miR-423-5p 敲低通过 GRIM-19 抑制 PC3 细胞的增殖并促进其凋亡。体内实验表明，miR-423-5p 抑制剂给药降低了裸鼠 PC 组织中的肿瘤体积，下调了 miR-423-5p 和 GRIM-19 的表达。