Dataset Information

Downregulation of miR-133a-3p promotes prostate cancer bone metastasis via activating PI3K/AKT signaling.

ABSTRACT:

Background

Bone metastasis is a leading cause of morbidity and mortality in advanced prostate cancer (PCa). Downexpression of miR-133a-3p has been found to contribute to the progression, recurrence and distant metastasis in PCa. However, clinical significance of miR-133a-3p in bone metastasis of PCa, and the biological role of miR-133a-3p and its molecular mechanisms underlying bone metastasis of PCa remain unclear.

Methods

miR-133a-3p expression was evaluated in 245 clinical PCa tissues by real-time PCR. Statistical analysis was performed to evaluate the clinical correlation between miR-133a-3p expression and clinicopathological features, and overall and bone metastasis-free survival in PCa patients. The biological roles of miR-133a-3p in the bone metastasis of PCa were investigated both in vitro and in vivo. Bioinformatics analysis, real-time PCR, western blot and luciferase reporter analysis were applied to demonstrate the relationship between miR-133a-3p and its potential targets. Western blotting and luciferase assays were examined to identify the underlying pathway involved in the anti-tumor role of miR-133a-3p. Clinical correlation of miR-133a-3p with its targets was verified in human PCa tissues.

Results

miR-133a-3p expression is reduced in PCa tissues compared with the adjacent normal tissues and benign prostate lesion tissues, particularly in bone metastatic PCa tissues. Low expression of miR-133a-3p is significantly correlated with advanced clinicopathological characteristics and shorter bone metastasis-free survival in PCa patients by statistical analysis. Moreover, upregulating miR-133a-3p inhibits cancer stem cell-like phenotypes in vitro and in vivo, as well as attenuates anoikis resistance in vitro in PCa cells. Importantly, administration of agomir-133a-3p greatly suppresses the incidence of PCa bone metastasis in vivo. Our results further demonstrate that miR-133a-3p suppresses bone metastasis of PCa via inhibiting PI3K/AKT signaling by directly targeting multiple cytokine receptors, including EGFR, FGFR1, IGF1R and MET. The negative clinical correlation of miR-133a-3p with EGFR, FGFR1, IGF1R, MET and PI3K/AKT signaling activity is determined in clinical PCa tissues.

Conclusion

Our results unveil a novel mechanism by which miR-133a-3p inhibits bone metastasis of PCa, providing the evidence that miR-133a-3p may serve as a potential bone metastasis marker in PCa, and delivery of agomir-133a-3p may be an effective anti-bone metastasis therapeutic strategy in PCa.

SUBMITTER: Tang Y

PROVIDER: S-EPMC6052526 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Publications

Downregulation of miR-133a-3p promotes prostate cancer bone metastasis via activating PI3K/AKT signaling.

Tang Yubo Y Pan Jincheng J Huang Shuai S Peng Xinsheng X Zou Xuenong X Luo Yongxiang Y Ren Dong D Zhang Xin X Li Ronggang R He Peiheng P Wa Qingde Q

Journal of experimental & clinical cancer research : CR 20180718 1

<h4>Background</h4>Bone metastasis is a leading cause of morbidity and mortality in advanced prostate cancer (PCa). Downexpression of miR-133a-3p has been found to contribute to the progression, recurrence and distant metastasis in PCa. However, clinical significance of miR-133a-3p in bone metastasis of PCa, and the biological role of miR-133a-3p and its molecular mechanisms underlying bone metastasis of PCa remain unclear.<h4>Methods</h4>miR-133a-3p expression was evaluated in 245 clinical PCa ...[more]

PMID: 30021600

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Dataset Information

Downregulation of miR-133a-3p promotes prostate cancer bone metastasis via activating PI3K/AKT signaling.

Background

Methods

Results

Conclusion

Publications

Downregulation of miR-133a-3p promotes prostate cancer bone metastasis via activating PI3K/AKT signaling.

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