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MiR-582-3p and miR-582-5p Suppress Prostate Cancer Metastasis to Bone by Repressing TGF-? Signaling.


ABSTRACT: A number of studies have reported that aberrant expression of microRNAs (miRNAs) closely correlates with the bone metastasis of prostate cancer (PCa). However, clinical significance and functional roles of both strands of a single miRNA in bone metastasis of PCa remain undefined. Here, we reported that miR-582-3p and miR-582-5p expression were simultaneously reduced in bone metastatic PCa tissues compared with non-bone metastatic PCa tissues. Downexpression of miR-582-3p and miR-582-5p strongly and positively correlated with advanced clinicopathological characteristics and shorter bone metastasis-free survival in PCa patients. Upregulating miR-582-3p and miR-582-5p inhibited invasion and migration abilities of PCa cells in vitro, as well as repressed bone metastasis in vivo. Our results further revealed that miR-582-3p and miR-582-5p attenuated bone metastasis of PCa via inhibiting transforming growth factor ? (TGF-?) signaling by simultaneously targeting several components of TGF-? signaling, including SMAD2, SMAD4, TGF-? receptor I (TGFBRI), and TGFBRII. Moreover, deletion contributes to miR-582-3p and miR-582-5p downexpression in PCa tissues. Finally, clinical negative correlations of miR-582-3p and miR-582-5p with SMAD2, SMAD4, TGFBRI, and TGFBRII were demonstrated in PCa tissues. Thus, our findings explore a novel tumor-suppressive miRNA with its both strands implicated in bone metastasis of PCa, suggesting its potential therapeutic value in treatment of PCa bone metastasis.

SUBMITTER: Huang S 

PROVIDER: S-EPMC6409413 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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miR-582-3p and miR-582-5p Suppress Prostate Cancer Metastasis to Bone by Repressing TGF-β Signaling.

Huang Shuai S   Zou Changye C   Tang Yubo Y   Wa Qingde Q   Peng Xinsheng X   Chen Xiao X   Yang Chunxiao C   Ren Dong D   Huang Yan Y   Liao Zhuangwen Z   Huang Sheng S   Zou Xuenong X   Pan Jincheng J  

Molecular therapy. Nucleic acids 20190115


A number of studies have reported that aberrant expression of microRNAs (miRNAs) closely correlates with the bone metastasis of prostate cancer (PCa). However, clinical significance and functional roles of both strands of a single miRNA in bone metastasis of PCa remain undefined. Here, we reported that miR-582-3p and miR-582-5p expression were simultaneously reduced in bone metastatic PCa tissues compared with non-bone metastatic PCa tissues. Downexpression of miR-582-3p and miR-582-5p strongly  ...[more]

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