Downregulation of miR-19a-3p promotes invasion, migration and bone metastasis via activating TGF-β signaling in prostate cancer

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.