Knockdown of Mediator Complex Subunit 19 Suppresses the Growth and Invasion of Prostate Cancer Cells.
Knockdown of Mediator Complex Subunit 19 Suppresses the Growth and Invasion of Prostate Cancer Cells.
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介导复合物亚基 19 的敲低可抑制前列腺癌细胞的生长和侵袭
DOI：
10.1371/journal.pone.0171134
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Wu J
中科院分区：
文献类型：
--
作者：
Yu S;Wang Y;Yuan H;Zhao H;Lv W;Chen J;Wan F;Liu D;Gao Z;Wu J
前列腺癌（PCa）是老年男性最常见的癌症之一。介体复合物亚基19（Med 19）在许多癌症中过表达并起促进作用。然而，Med 19在PCa中的作用仍然不清楚。在本研究中，我们通过免疫组织化学染色，发现Med 19在PCa组织中的表达水平高于邻近的良性前列腺组织。然后，我们通过使用慢病毒siRNA敲低PCa细胞系LNCaP和PC 3中的Med 19表达。Med 19敲除PCa细胞的增殖、锚定非依赖性生长、迁移和侵袭受到抑制。在裸鼠异种移植模型中，我们发现Med 19敲低PCa细胞形成的肿瘤比对照细胞更小，增殖指数更低。在机制研究中，我们发现Med 19可以调节参与细胞增殖、细胞周期和上皮-间质转化的基因，包括P27、pAKT、pPI 3 K、IGF 1 R、E-Cadherin、N-Cadherin、Vimentin、ZEB 2、Snail-1和Snail-2。以Med 19为靶点，可以抑制PCa的生长和转移，有望成为治疗PCa的新方法。
Prostate cancer (PCa) is one of the most common cancers in elderly men. Mediator Complex Subunit 19 (Med19) is overexpressed and plays promotional roles in many cancers. However, the roles of Med19 in PCa are still obscure. In this study, by using immunohistochemical staining, we found higher expression level of Med19 in PCa tissues than in adjacent benign prostate tissues. We then knocked down the Med19 expression in PCa cell lines LNCaP and PC3 by using lentivirus siRNA. Cell proliferation, anchor-independent growth, migration, and invasion were suppressed in Med19 knockdown PCa cells. In nude mice xenograft model, we found that Med19 knockdown PCa cells formed smaller tumors with lower proliferation index than did control cells. In the mechanism study, we found that Med19 could regulate genes involved in cell proliferation, cell cycle, and epithelial-mesenchymal transition, including P27, pAKT, pPI3K, IGF1R, E-Cadherin, N-Cadherin, Vimentin, ZEB2, Snail-1 and Snail-2. Targeting Med19 in PCa cells could inhibit the PCa growth and metastasis, and might be a therapeutic option for PCa in the future.