Affiliations: [a] Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China | [b] Department of Urology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, China
Correspondence:
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Corresponding author: Ranlu Liu, Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China. Tel.: +86 22 8832969; E-mail: [email protected].
Note: [1] Zhenpeng Lian and Taihao Chang contributed equally to this work.
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.
