Knockdown of Mediator Complex Subunit 19 Suppresses the Growth and Invasion of Prostate Cancer Cells

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.

前列腺癌（Prostate cancer, PCa）是老年男性最常见的恶性肿瘤之一。中介体复合物亚基19（Mediator Complex Subunit 19, Med19）在多种癌症中呈高表达状态，并发挥促癌作用。然而，Med19在前列腺癌中的具体作用仍有待阐明。本研究通过免疫组织化学染色发现，前列腺癌组织中Med19的表达水平显著高于邻近良性前列腺组织。随后，我们利用慢病毒小干扰RNA（lentivirus siRNA）敲低前列腺癌细胞系LNCaP与PC3中Med19的表达。实验结果显示，敲低Med19的前列腺癌细胞的增殖、非锚定依赖性生长、迁移及侵袭能力均受到显著抑制。在裸鼠异种移植瘤模型中，相较于对照组细胞，敲低Med19的前列腺癌细胞形成的肿瘤体积更小，且增殖指数更低。机制研究表明，Med19可调控参与细胞增殖、细胞周期及上皮间质转化（Epithelial-Mesenchymal Transition, EMT）的相关基因，包括P27、pAKT、pPI3K、IGF1R、E-钙粘蛋白（E-Cadherin）、N-钙粘蛋白（N-Cadherin）、波形蛋白（Vimentin）、ZEB2、Snail-1及Snail-2。靶向Med19可抑制前列腺癌的生长与转移，有望在未来成为前列腺癌的潜在治疗策略。