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miR-582-3p and miR-582-5p Suppress Prostate Cancer Metastasis to Bone by Repressing TGF-β 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 β (TGF-β) signaling by simultaneously targeting several components of TGF-β signaling, including SMAD2, SMAD4, TGF-β 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.

journal_name

Mol Ther Nucleic Acids

journal_title

Molecular therapy. Nucleic acids

authors

Huang S,Zou C,Tang Y,Wa Q,Peng X,Chen X,Yang C,Ren D,Huang Y,Liao Z,Huang S,Zou X,Pan J

doi

10.1016/j.omtn.2019.01.004

subject

Has Abstract

pub_date

2019-06-07 00:00:00

pages

91-104

issn

2162-2531

pii

S2162-2531(19)30007-1

journal_volume

16

pub_type

杂志文章

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