Department of Orthopaedic Surgery, The Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563003, P.R. China.
Department of Pelvic Floor Center, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510655, P.R. China.
Oncol Rep. 2018 Jan;39(1):81-90. doi: 10.3892/or.2017.6096. Epub 2017 Nov 13.
Constitutive activation of TGF‑β signaling pathway is a well-documented mechanism responsible for the bone metastasis of prostate cancer (PCa). MicroRNAs (miRNAs) have been reported to be crucial for the activation of TGF‑β signaling via targeting downstream components of TGF‑β signaling pathway. Here, we report that miR‑19a‑3p is downregulated in bone metastatic PCa tissues and cells. Upregulation of miR‑19a‑3p suppresses invasion, migration in vitro and inhibits bone metastasis in vivo in PCa cells. Conversely, silencing miR‑19a‑3p yields the opposite effect. Our results further demonstrate that miR‑19a‑3p inhibits invasion and migration abilities of PCa cells via targeting downstream effectors of TGF‑β signaling, SMAD2 and SMAD4, resulting in the inactivation of TGF‑β signaling. Therefore, our results uncover a novel mechanistic understanding of miR‑19a‑3p-induced suppressive role in bone metastasis of PCa, which will facilitate the development of effective cancer therapy methods against PCa.
TGF-β 信号通路的组成性激活是导致前列腺癌（PCa）骨转移的一个有充分文献记录的机制。已经有报道称，microRNAs（miRNAs）通过靶向 TGF-β 信号通路的下游成分，对于 TGF-β 信号的激活至关重要。在这里，我们报告 miR-19a-3p 在骨转移的 PCa 组织和细胞中下调。miR-19a-3p 的上调抑制了 PCa 细胞的体外侵袭和迁移，并抑制了体内骨转移。相反，沉默 miR-19a-3p 则产生相反的效果。我们的结果进一步表明，miR-19a-3p 通过靶向 TGF-β 信号的下游效应物 SMAD2 和 SMAD4，抑制 PCa 细胞的侵袭和迁移能力，从而使 TGF-β 信号失活。因此，我们的结果揭示了 miR-19a-3p 在抑制 PCa 骨转移中的作用的新机制理解，这将有助于开发针对 PCa 的有效癌症治疗方法。
