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miR-138 通过 Wnt/β-catenin 通路调节前列腺癌细胞的侵袭和迁移。

miR‑138 modulates prostate cancer cell invasion and migration via Wnt/β‑catenin pathway.

机构信息

Department of Urology, Eighth People's Hospital of Shanghai, Shanghai 200233, P.R. China.

出版信息

Mol Med Rep. 2018 Feb;17(2):3140-3145. doi: 10.3892/mmr.2017.8273. Epub 2017 Dec 12.

Abstract

The prognosis for prostate cancer patients with distant metastasis is poor, with an average survival rate of 24‑48 months. The exact mechanisms underlying prostate cancer metastasis remain to be elucidated, despite previous research efforts. The present study aimed to reveal the regulatory roles of miR‑138 via Wnt/β‑catenin pathway in prostate cancer cell migration and invasion. Reverse transcription‑quantitative polymerase chain reaction was used to examine the mRNA and protein expression levels and transwell assay was conducted to determine cell invasion and migration. A luciferase reporter assay was used to determine the target association between miR‑138 and β‑catenin. The present study identified microRNA (miR)‑138 as an invasion and migration regulator in prostate cancer. miR‑138 was downregulated in aggressive prostate cancer cell lines. Furthermore, followingmiR‑138 overexpression, prostate cancer cells exhibited impaired invasive and migratory abilities. E‑cadherin was upregulated and vimentin was downregulated. In addition, it was demonstrated that miR‑138 negatively regulated the Wnt/β‑catenin pathway activation in prostate cancer. The pathway was then activated via β‑catenin overexpression and this reversed the effects of miR‑138. The results suggest that miR‑138 downregulation may contribute to prostate cancer progression and metastasis. The findings provide a novel molecular therapeutic target in the treatment of prostate cancer metastasis.

摘要

前列腺癌伴远处转移患者的预后较差,平均存活时间为 24-48 个月。尽管之前进行了大量研究,但前列腺癌转移的确切机制仍有待阐明。本研究旨在通过 Wnt/β-catenin 通路揭示 miR-138 在前列腺癌细胞迁移和侵袭中的调控作用。逆转录定量聚合酶链反应用于检测 mRNA 和蛋白表达水平,Transwell 测定用于检测细胞侵袭和迁移。荧光素酶报告基因测定用于确定 miR-138 与β-catenin 之间的靶标关联。本研究确定了 microRNA (miR)-138 是前列腺癌的侵袭和迁移调节剂。miR-138 在侵袭性前列腺癌细胞系中下调。此外,过表达 miR-138 后,前列腺癌细胞的侵袭和迁移能力受损。E-钙黏蛋白上调,波形蛋白下调。此外,研究表明 miR-138 负调控前列腺癌中 Wnt/β-catenin 通路的激活。然后通过β-catenin 过表达激活该通路,从而逆转了 miR-138 的作用。结果表明,miR-138 的下调可能导致前列腺癌的进展和转移。这些发现为治疗前列腺癌转移提供了新的分子治疗靶点。

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