Knockdown of Med19 Suppresses Proliferation and Enhances Chemo-sensitivity to Cisplatin in Non-small Cell Lung Cancer Cells

Wei, Ling; Wang, Xing-Wu; Sun, Jian; Lv, Li; Xie, Li; Song, Xianrang

doi:10.7314/apjcp.2015.16.3.875

Cited by 11 publications

(13 citation statements)

References 34 publications

(13 reference statements)

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“…In breast cancer, Med19 may promote cell proliferation by regulating CBFA2T3/HEB expression [ 13 ]. 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 ].…”

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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“…20,[23][24][25][26][27] Additionally, Med19 upregulation in non-small-cell lung cancer cells (NSCLC) contributes to resistance to the chemotherapeutic drugs cisplatin (DDP) and taxol (TAX). 28 We recently confirmed that an increase in Med19 expression is evident in ADM-resistant human breast cancer cells (MCF-7/ADM) compared with parental MCF-7 cells. In addition, Med19 expression is significantly increased in ADMresistant tissues compared with that in ADM-sensitive tissues.…”

mentioning

confidence: 54%

“…Previous research have shown that activation of autophagy enhanced chemoresistance in various cancers. Wei et al reported that the induction of autophagy promoted NSCLC resistance to DDP. Another study revealed that suppression of autophagy with a chemical inhibitor, chloroquine, increased the apoptosis caused by ADM and enhanced chemosensitivity to ADM in prostate cancer cells .…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have implicated Med19 in the oncogenesis of several human carcinoma types, including gastric cancer, colorectal cancer, bladder cancer, osteosarcoma, hepatocellular cancer, and laryngocarcinoma . Additionally, Med19 upregulation in non–small‐cell lung cancer cells (NSCLC) contributes to resistance to the chemotherapeutic drugs cisplatin (DDP) and taxol (TAX) . We recently confirmed that an increase in Med19 expression is evident in ADM‐resistant human breast cancer cells (MCF‐7/ADM) compared with parental MCF‐7 cells.…”

Section: Introductionmentioning

confidence: 99%

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Med19 is involved in chemoresistance by mediating autophagy through HMGB1 in breast cancer

Liu

Zhang

et al. 2018

J of Cellular Biochemistry

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Adriamycin (ADM)-based regimens are the most effective chemotherapeutic treatments for breast cancer. However, intrinsic and acquired chemoresistance is a major therapeutic problem. Our goal was to clarify the role of mediator complex subunit 19 (Med19) in chemotherapy resistance and to elucidate the related molecular mechanisms. In this study, ADM-resistant human cells (MCF-7/ADM) and tissues exhibited increased Med19 expression and autophagy levels relative to the corresponding control groups. Additionally, MCF-7/ADM cells showed changes in two selective markers of autophagy. There was a dose-dependent increase in the light chain 3 (LC3)-II/LC3-I ratio and a decrease in sequestosome 1 (P62/SQSTMl) expression. Furthermore, lentivirus-mediated Med19 inhibition significantly attenuated the LC3-II/LC3-I ratio, autophagy-related gene 3 (Atg3) and autophagy-related gene 5 (Atg5) expression, P62 degradation, and red fluorescent protein-LC3 dot formation after treatment with ADM or rapamycin, an autophagy activator. Furthermore, the antiproliferative effects of ADM, cisplatin (DDP), and taxol (TAX) were significantly enhanced after suppressing Med19 expression. Notably, the effects of Med19 on autophagy were mediated through the high-mobility group box-1 (HMGB1) pathway. Our findings suggest that Med19 suppression increased ADM chemosensitivity by downregulating autophagy through the inhibition of HMGB1 signaling in human breast cancer cells. Thus, the regulatory mechanisms of Med19 in autophagy should be investigated to reduce tumor resistance to chemotherapy.

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“…No studies have yet directly linked MED19 to regulation of ER activity in breast cancer, unlike AR in prostate cancer. Emerging evidence points to a role for MED19 in many types of cancer, and future studies will likely shed light onto its mechanism of action in endocrine and other cancers [42, 55, 56].…”

Section: Mediator and Endocrine Cancersmentioning

confidence: 99%

The mediator complex in genomic and non-genomic signaling in cancer

Weber

Garabedian

2018

Steroids

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Mediator is a conserved, multi-subunit macromolecular machine divided structurally into head, middle, and tail modules, along with a transiently associating kinase module. Mediator functions as an integrator of transcriptional regulatory activity by interacting with DNA-bound transcription factors and with RNA polymerase II (Pol II) to both activate and repress gene expression. Mediator has been shown to affect multiple steps in transcription, including chromatin looping between enhancers and promoters, pre-initiation complex formation, transcriptional elongation, and mRNA splicing. Individual Mediator subunits participate in regulation of gene expression by the estrogen and androgen receptors and are altered in a number of endocrine cancers, including breast and prostate cancer. In addition to its role in genomic signaling, MED12 has been implicated in non-genomic signaling by interacting with and activating TGF-beta receptor 2 in the cytoplasm. Recent structural studies have revealed extensive inter-domain interactions and complex architecture of the Mediator-Pol II complex, suggesting that Mediator is capable of reorganizing its conformation and composition to fit cellular needs. We propose that alterations in Mediator subunit expression that occur in various cancers could impact the organization and function of Mediator, resulting in changes in gene expression that promote malignancy. A better understanding of the role of Mediator in cancer could reveal new approaches to the diagnosis and treatment of Mediator-dependent endocrine cancers, especially in settings of therapy resistance.

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Knockdown of Med19 Suppresses Proliferation and Enhances Chemo-sensitivity to Cisplatin in Non-small Cell Lung Cancer Cells

Cited by 11 publications

References 34 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

Med19 is involved in chemoresistance by mediating autophagy through HMGB1 in breast cancer

The mediator complex in genomic and non-genomic signaling in cancer

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