Ectopic Expression of miR-532-3p Suppresses Bone Metastasis of Prostate Cancer Cells via Inactivating NF-κB Signaling

• Main Authors: Qingde Wa, Changye Zou, Zhuoyuan Lin, Sheng Huang, Xinsheng Peng, Chunxiao Yang, Dong Ren, Dongchu Xu, Yuanqing Guo, Zhuangwen Liao, Bin Wang, Hailan Hu, Shuai Huang, Peiheng He
• Format: Article
• Language: English
• Published: Elsevier 2020-06-01
• Series: Molecular Therapy: Oncolytics
• Subjects: miR-532-3p; bone metastasis; NF-κB signaling; prostate cancer
• Online Access: http://www.sciencedirect.com/science/article/pii/S2372770520300498

miR-532-3p is a widely documented microRNA (miRNA) involved in multifaceted processes of cancer tumorigenesis and metastasis. However, the clinical significance and biological functions of miR-532-3p in bone metastasis of prostate cancer (PCa) remain largely unknown. Herein, we report that miR-532-3p was downregulated in PCa tissues with bone metastasis, and downexpression of miR-532-3p was significantly associated with Gleason grade and serum prostate-specific antigen (PSA) levels and predicted poor bone metastasis-free survival in PCa patients. Upregulating miR-532-3p inhibited invasion and migration abilities of PCa cells in vitro, while silencing miR-532-3p yielded an opposite effect on invasion and migration abilities of PCa cells. Importantly, upregulating miR-532-3p repressed bone metastasis of PCa cells in vivo. Our results further demonstrated that overexpression of miR-532-3p inhibited activation of nuclear facto κB (NF-κB) signaling via simultaneously targeting tumor necrosis factor receptor-associated factor 1 (TRAF1), TRAF2, and TRAF4, which further promoted invasion, migration, and bone metastasis of PCa cells. Therefore, our findings reveal a novel mechanism contributing to the sustained activity of NF-κB signaling underlying the bone metastasis of PCa.