通过NF-κB调节，miR-96-5p诱导的NDRG1缺乏促进前列腺癌侵袭。

Prostate cancer invasion is promoted by the miR-96-5p-induced NDRG1 deficiency through NF-κB regulation.

作者信息

Soror A A, Eshagh R, Fahim M R, Jamshidian A, Monfared G H

出版信息

Klin Onkol. 2024;38(2):95-101. doi: 10.48095/ccko202495.

DOI:10.48095/ccko202495

PMID:38697817

Abstract

BACKGROUND

The N-myc downstream-regulated gene 1 (NDRG1) has been discovered as a significant gene in the progression of cancers. However, the regulatory mechanism of NDRG1 remained obscure in prostate cancer (PCa).

METHODS

The miR-96-5p and NDRG1 expression levels were evaluated in PCa cell lines, and prostate tissues, and validated in public databases by real-time polymerase chain reaction, western blot analysis, and immunohistochemistry. The function of miR-96-5p and NDRG1 were investigated by scratch assay and transwell assays in vitro, and mouse xenograft assay in vivo. The candidate pathway regulated by NDRG1 was conducted by the next-generation gene sequencing technique. Immunofluorescence and luciferase assays were used to detect the relation between miR-96-5p, NDRG1, and NF-kB pathway.

RESULTS

Overexpressing NDRG1 suppresses the migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro, and inhibits metastasis in vivo. Moreover, miR-96-5p contributes to NDRG1 deficiency and promotes PCa cell migration and invasion. Furthermore, NDRG1 loss activates the NF-kB pathway, which stimulates p65 and IKBa phosphorylation and induces EMT in PCa.

CONCLUSIONS

MiR-96-5p promotes the migration and invasion of PCa by targeting NDRG1 and regulating the NF-kB pathway.

摘要

背景

N-myc下游调控基因1（NDRG1）已被发现是癌症进展中的一个重要基因。然而，NDRG1在前列腺癌（PCa）中的调控机制仍不清楚。

方法

通过实时聚合酶链反应、蛋白质免疫印迹分析和免疫组织化学，评估PCa细胞系和前列腺组织中miR-96-5p和NDRG1的表达水平，并在公共数据库中进行验证。通过体外划痕试验和Transwell试验以及体内小鼠异种移植试验研究miR-96-5p和NDRG1的功能。采用下一代基因测序技术研究NDRG1调控的候选通路。用免疫荧光和荧光素酶试验检测miR-96-5p、NDRG1与NF-κB通路之间的关系。