Knockdown of mediator complex subunit 19 inhibits the growth of ovarian cancer

Liu, Yingtao; Tao, Xiang; Fan, Lingling; Jia, Luoqi; Gu, Chao; Yan, Feng

doi:10.3892/mmr.2012.1065

Cited by 10 publications

(5 citation statements)

References 19 publications

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“…In lung cancer, MED19 could promote tumor proliferation, tumorigenesis, metastasis, and enhance chemo-sensitivity to cisplatin in non-small cell lung cancer cells [ 14 – 16 ]. The Med19 has been reported to promote tumor growth and/or metastasis in ovarian cancer, gastric cancer, pancreatic cancer, osteosarcoma, and liver cancer [ 5 – 7 , 17 – 18 ]. However, there are few reports about the roles of Med19 in PCa.…”

Section: Discussionmentioning

confidence: 99%

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

Wang

Yuan

et al. 2017

PLoS ONE

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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.

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Section: Discussionmentioning

confidence: 99%

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

Wang

Yuan

et al. 2017

PLoS ONE

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“…Thus, MED19 is known to be closely related to the mechanism and development of cancer, and the elevated expression of MED19 in tumor cells or tissues indicates a poor prognosis of patients. MED19 has been shown to be involved in the process of tumor cell proliferation, invasion, migration, cell cycle regulation, and apoptosis, 62,63 indicating that MED19 might be a potential target for tumor diagnosis, targeted therapy, and prognosis. However, until now, the role of MED19 in tumor signaling pathway and its upstream and downstream target genes has not been fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

The role of mediator complex subunit 19 in human diseases

Zhang

Qin

Yan

et al. 2021

Exp Biol Med (Maywood)

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Mediator is an evolutionarily conserved multi-protein complex that mediates the interaction between different proteins as a basic linker in the transcription mechanism of eukaryotes. It interacts with RNA polymerase II and participates in the process of gene expression. Mediator complex subunit 19 or regulation by oxygen 3, or lung cancer metastasis-related protein 1 is located at the head of the mediator complex; it is a multi-protein co-activator that induces the transcription of RNA polymerase II by DNA transcription factors. It is a tumor-related gene that plays an important role in transcriptional regulation, cell proliferation, and apoptosis and is closely related to the occurrence and development of the cancers of the lung, bladder, skin, etc. Here, we used the structure of mediator complex subunit 19 to review its role in tumor progression, fat metabolism, drug therapy, as well as the novel coronavirus, which has attracted much attention at present, suggesting that mediator complex subunit 19 has broad application in the occurrence and development of clinical diseases. As a tumor-related gene, the role and mechanism of mediator complex subunit 19 in the regulation of tumor growth could be of great significance for the diagnosis, prognosis, and treatment of mediator complex subunit 19 -related tumors.

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“…Our study may also have implications for MED19 function in other cancers. For example, reduction of MED19 by siRNA has been reported to reduce the proliferation of certain breast, ovarian, cervical, and lung cancer cell lines, and increased abundance of MED19 protein is observed in tumors relative to benign tissue [55–62]. This suggests that MED19 functions with other transcription factors in other cell types to regulate gene expression and enhance cellular proliferation.…”

Section: Discussionmentioning

confidence: 99%

MED19 alters AR occupancy and gene expression in prostate cancer cells, driving MAOA expression and growth under low androgen

Weber

Ruoff

Garabedian

2019

Preprint

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Androgen deprivation therapy (ADT) is a mainstay of prostate cancer treatment, given the dependence of prostate cells on androgen and the androgen receptor (AR). However, tumors become ADT-resistant, and there is a need to understand the mechanism. One possible mechanism is the upregulation of AR co-regulators, although only a handful have been definitively linked to disease. We previously identified the Mediator subunit MED19 as an AR co-regulator, and reported that MED19 depletion inhibits AR transcriptional activity and growth of androgen-insensitive LNCaP-abl cells. Therefore, we proposed that MED19 upregulation would promote AR activity and drive androgen-independent growth. Here, we show that stable overexpression of MED19 in androgen-dependent LNCaP cells promotes growth under conditions of androgen deprivation. To delineate the mechanism, we determined the MED19 and AR transcriptomes and cistromes in control and MED19 LNCaP cells. We also examined H3K27 acetylation genome-wide. MED19 overexpression selectively alters AR occupancy, H3K27 acetylation, and gene expression. Under conditions of androgen deprivation, genes regulated by MED19 and genomic sites occupied by MED19 and AR are enriched for ELK1, a transcription factor that binds the AR N-terminus to promote select AR-target gene expression. Strikingly, MED19 upregulates expression of monoamine oxidase A (MAOA), a factor that promotes prostate cancer growth. MAOA depletion reduces androgen-independent growth. MED19 and AR occupy the MAOA promoter, with MED19 overexpression enhancing AR occupancy and H3K27 acetylation. Furthermore, MED19 overexpression increases ELK1 occupancy at the MAOA promoter, and ELK1 depletion reduces MAOA expression and androgen-independent growth. This suggests that MED19 cooperates with ELK1 to regulate AR occupancy and H3K27 acetylation at MAOA, upregulating its expression and driving androgen independence in prostate cancer cells. This study provides important insight into the mechanisms of prostate cancer cell growth under low androgen, and underscores the importance of the MED19-MAOA axis in this process.Author summaryProstate cancer is one of the most common cancers worldwide, and androgen hormones are essential for prostate cancer growth. Androgens exert their effects through a protein called the androgen receptor (AR), which turns on and off genes that regulate prostate cancer growth. Powerful drugs that block AR action by lowering androgen levels – so-called androgen deprivation therapy - are used to treat prostate cancer patients, and these yield initial success in reducing tumor growth. However, over time, tumors circumvent androgen deprivation therapy and patients relapse; in many cases, this occurs because AR becomes re-activated. The factors responsible for re-activating AR and promoting growth under androgen deprivation are not well understood. Here, we demonstrate that a subunit of the Mediator transcriptional regulatory complex, called MED19, promotes growth of prostate cancer cells under low androgen conditions, mimicking the ability of tumors to grow under androgen deprivation in prostate cancer patients. MED19 promotes androgen-independent growth by working with a transcription factor that interacts with AR, called ELK1, to induce the expression of genes regulated by AR that promote prostate cancer growth. This study provides important insight into how prostate cancer cells can maintain growth under androgen deprivation through MED19.

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Knockdown of mediator complex subunit 19 inhibits the growth of ovarian cancer

Cited by 10 publications

References 19 publications

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

The role of mediator complex subunit 19 in human diseases

MED19 alters AR occupancy and gene expression in prostate cancer cells, driving MAOA expression and growth under low androgen

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