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

Wa,Qingde; Li,Li; Lin,Hongcheng; Peng,Xinsheng; Ren,Dong; Huang,Yan; He,Peiheng; Huang,Shuai

doi:10.3892/or.2017.6096

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

Authors:
- Qingde Wa
- Li Li
- Hongcheng Lin
- Xinsheng Peng
- Dong Ren
- Yan Huang
- Peiheng He
- Shuai Huang
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Affiliations: 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, Department of Orthopaedic Surgery/Orthopaedic Research Institute, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Orthopaedic Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, P.R. China
Published online on: November 13, 2017 https://doi.org/10.3892/or.2017.6096
Pages: 81-90
Copyright: © Wa et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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