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

Date Published: January 26, 2017

Publisher: Public Library of Science

Author(s): Shengqiang Yu, Yanwei Wang, Hejia Yuan, Hongwei Zhao, Wei Lv, Jian Chen, Fengchun Wan, Dongfu Liu, Zhenli Gao, Jitao Wu, Aamir Ahmad.

http://doi.org/10.1371/journal.pone.0171134

Abstract

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.

Partial Text

Prostate cancer (PCa) is one of the most common cancers in western world, with a leading cause of mortality and morbidity [1]. Early detection and treatment have improved the survival rate significantly. However, 20~40% of patients undergoing radical prostatectomy and 30~50% of patients undergoing radiotherapy will have biochemical recurrence within 10 years [2]. For advanced PCa, androgen deprivation therapy (ADT) is still the first therapeutic option [3]. Although initially effective at blocking tumor progression, ADT eventually fails by leading PCa to a castration-resistant stage. Many efforts have been made to seek more effective therapeutic methods for PCa [4].

Med19 is a component of the Mediator complex, which involved in the transcription regulation of nearly all RNA polymerase II-dependent genes [10]. Med19 is important in stabilizing the entire Mediator complex, making it critical to the transcriptional regulation [11]. Absence of Med19 may decrease the binding affinity of Mediator with RNA Polymerase II [11].

 

Source:

http://doi.org/10.1371/journal.pone.0171134

 

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