Ectopic Expression of miR-532-3p Suppresses Bone Metastasis of Prostate Cancer Cells via Inactivating NF-κB Signaling
Ectopic Expression of miR-532-3p Suppresses Bone Metastasis of Prostate Cancer Cells via Inactivating NF-κB Signaling
复制标题
miR-532-3p 的异位表达通过失活 NF-kappa B 信号抑制前列腺癌细胞的骨转移
DOI：
10.1016/j.omto.2020.03.024
复制
发表时间：
2020-06-26
影响因子：
5.7
通讯作者：
He, Peiheng
中科院分区：
文献类型：
--
作者：
Wa, Qingde;Zou, Changye;He, Peiheng
miR-532- 3 p是一种被广泛报道的microRNA（miRNA），参与癌症肿瘤发生和转移的多方面过程。然而，miR-532- 3 p在前列腺癌骨转移中的临床意义和生物学功能尚不清楚。在此，我们报道了miR-532- 3 p在有骨转移的PCa组织中下调，并且miR-532- 3 p的下调与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患者的无骨转移生存率。上调miR-532- 3 p抑制PCa细胞的体外侵袭和迁移能力，而沉默miR-532- 3 p则对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- 3 p在体内抑制了PCa细胞的骨转移。我们的研究结果进一步表明，miR-532- 3 p的过表达通过同时靶向肿瘤坏死因子受体相关因子1（TRAF 1）、TRAF 2和TRAF 4抑制核因子κ B（NF-κ B B）信号的激活，从而进一步促进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新的机制，有助于持续活性的NF-κ B信号的骨转移的前列腺癌。
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 metastasisfree 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 kappa B (NF-kappa B) 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-kappa B signaling underlying the bone metastasis of PCa.