2014Molecular CarcinogenesisRequires access

MiR‐130b suppresses prostate cancer metastasis through down‐regulation of MMP2

Qin Chen, Xian Zhao, Hailong Zhang, Haihua Yuan, Miaojun Zhu, Qian Sun, Xueping Lai, Yanli Wang, Jian Huang, Jianshe Yan, Jianxiu Yu

Open publisher page 75 citations

Abstract

Prostate cancer (PCa) is the most prevalent malignant carcinoma among males in western countries. Currently no treatments can cure advanced prostate cancers, so new diagnostic and therapeutic strategies are in urgent need. At present limited knowledge is available concerning the roles of dysregulated microRNAs in prostate cancer metastasis. In this study, we found that the expression of miR-130b was significantly down-regulated in prostate cancer cell lines and clinical prostate cancer tissues. Enforced over-expression of miR-130b in prostate cancer cells suppressed whereas knock-down of miR-130b increased cell migration and invasion. Using mouse model, we revealed that miR-130b-expressed prostate cancer cells displayed significant reduction in tumor metastasis. Furthermore, we identified and validated matrix metalloproteinase-2 (MMP2) as a direct target of miR-130b. Ectopic expression of MMP2 rescued miR-130b-suppressed cell migration and invasion, and knock-down of MMP2 antagonized the effect of silencing miR-130b.Taken together, our data reveal for the first time that miR-130b exerts a suppressive effect in prostate cancer metastasis through down-regulation of MMP2.

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What this paper is about

Prostate cancer (PCa) is the most prevalent malignant carcinoma among males in western countries. Currently no treatments can cure advanced prostate cancers, so new diagnostic and therapeutic strategies are in urgent need. At present limited knowledge is available concerning the roles of dysregulated microRNAs in prostate cancer metastasis. In this study, we found that the expression of miR-130b was significantly down-regulated in prostate cancer cell lines and clinical prostate cancer tissues. Enforced over-expression of miR-130b in prostate cancer cells suppressed whereas knock-down of miR-130b increased cell migration and invasion. Using mouse model, we revealed that miR-130b-expressed prostate cancer cells displayed significant reduction in tumor metastasis. Furthermore, we identified and validated matrix metalloproteinase-2 (MMP2) as a direct target of miR-130b. Ectopic expression of MMP2 rescued miR-130b-suppressed cell migration and invasion, and knock-down of MMP2 antagonized the effect of silencing miR-130b.Taken together, our data reveal for the first time that miR-130b exerts a suppressive effect in prostate cancer metastasis through down-regulation of MMP2.

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Available abstract

Prostate cancer (PCa) is the most prevalent malignant carcinoma among males in western countries. Currently no treatments can cure advanced prostate cancers, so new diagnostic and therapeutic strategies are in urgent need. At present limited knowledge is available concerning the roles of dysregulated microRNAs in prostate cancer metastasis. In this study, we found that the expression of miR-130b was significantly down-regulated in prostate cancer cell lines and clinical prostate cancer tissues. Enforced over-expression of miR-130b in prostate cancer cells suppressed whereas knock-down of miR-130b increased cell migration and invasion. Using mouse model, we revealed that miR-130b-expressed prostate cancer cells displayed significant reduction in tumor metastasis. Furthermore, we identified and validated matrix metalloproteinase-2 (MMP2) as a direct target of miR-130b. Ectopic expression of MMP2 rescued miR-130b-suppressed cell migration and invasion, and knock-down of MMP2 antagonized the effect of silencing miR-130b.Taken together, our data reveal for the first time that miR-130b exerts a suppressive effect in prostate cancer metastasis through down-regulation of MMP2.

Key concepts: MMP2, Prostate cancer, Metastasis, Cancer research, Gene silencing, Cancer, Biology, Ectopic expression

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