Affiliation:
1. Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China
2. Department of Urology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, China
Abstract
OBJECTIVE: 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, prostate tissues, and validated public databases by real-time PCR, western blot analysis, and immunohistochemistry. The function of miR-96-5p and NDRG1 were investigated by wound healing 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 assay was used to detect the relation between miR-96-5p, NDRG1, and NF-κB 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-κB 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-κB pathway.
Subject
Cancer Research,Genetics,Oncology,General Medicine