Wa Qingde, Zou Changye, Lin Zhuoyuan, Huang Sheng, Peng Xinsheng, Yang Chunxiao, Ren Dong, Xu Dongchu, Guo Yuanqing, Liao Zhuangwen, Wang Bin, Hu Hailan, Huang Shuai, He Peiheng
Department of Orthopedic Surgery, The Affiliated Hospital of Zunyi Medical College, Zunyi 563003, China.
Department of Orthopedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
Mol Ther Oncolytics. 2020 Apr 7;17:267-277. doi: 10.1016/j.omto.2020.03.024. eCollection 2020 Jun 26.
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 , 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 . 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.
miR-532-3p是一种有广泛文献记载的微小RNA（miRNA），参与癌症肿瘤发生和转移的多方面过程。然而，miR-532-3p在前列腺癌（PCa）骨转移中的临床意义和生物学功能仍 largely未知。在此，我们报告miR-532-3p在发生骨转移的PCa组织中表达下调，且miR-532-3p的低表达与Gleason分级和血清前列腺特异性抗原（PSA）水平显著相关，并预测PCa患者无骨转移生存期较差。上调miR-532-3p可抑制PCa细胞的侵袭和迁移能力，而沉默miR-532-3p对PCa细胞的侵袭和迁移能力产生相反的影响。重要的是，上调miR-532-3p可抑制PCa细胞的骨转移。我们的结果进一步证明，miR-532-3p的过表达通过同时靶向肿瘤坏死因子受体相关因子1（TRAF1）、TRAF2和TRAF4抑制核因子κB（NF-κB）信号通路的激活，而这进一步促进了PCa细胞的侵袭、迁移和骨转移。因此，我们的研究结果揭示了一种导致PCa骨转移中NF-κB信号通路持续激活的新机制。
