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Downregulation of MED12 via siRNA in prostate cancer cell lines (3’ tag DGE)

ABSTRACT: The Mediator complex is a multi-subunit protein that modulates gene expression on a genome-wide scale. MED12 and cyclin-dependent kinase 8 (CDK8) or its paralog CDK19 are components of its kinase module that regulate the proliferation of prostate cancer cells. In this study, we investigated how MED12 and CDK8/19 influence cancer-driven processes in prostate cancer cell lines, focusing on AR activity and enzalutamide resistance.

ORGANISM(S): Homo sapiens

PROVIDER: GSE269072 | GEO | 2024/09/26

REPOSITORIES: GEO

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Downregulation of MED12 via siRNA in SPHEROIDS derived from prostate cancer cell lines (3’ tag DGE)

Project description:The Mediator complex is a multi-subunit protein that modulates gene expression on a genome-wide scale. MED12 and cyclin-dependent kinase 8 (CDK8) or its paralog CDK19 are components of its kinase module that regulate the proliferation of prostate cancer cells. In this study, we investigated how MED12 and CDK8/19 influence cancer-driven processes in prostate cancer cell lines, focusing on AR activity and enzalutamide resistance.

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Interactions of CDK19 with MED12 and cyclin-C assessed by chemical cross-linking mass spectrometry

Project description:Chemical cross-linking coupled to mass spectrometry was used to study binary and ternary complexes involving cyclin-dependent kinase 19 (CDK19), cyclin-C, and an N-terminal fragment of subunit 12 of the Mediator complex (MED12 1-100). Cross-linking was performed using disuccinimidyl suberate (DSS). These results were generated in the context of the study published as Klatt et al., A precisely positioned MED12 activation helix stimulates CDK8 kinase activity, Proc. Natl. Acad. Sci. USA 2020 (DOI: 10.1073/pnas.1917635117) with the associated data set PXD015394, but were not included in the article.

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Requirement for the Mediator kinase module for activation of super-enhancer associated genes in colon cancer cells

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Cdk8, Cyclin C, Med12 or Med13 depletion effect on gene expression in Drosophila S2 cells

Project description:Expression profiling following depletion of Mediator Cdk8 module subunits Cdk8, Cyclin C (CycC), Med12 and Med13 72 hours after dsRNA treatment of Drosophila melanogaster S2 cells. Results provide insight into the role of individual Cdk8 module subunits in regulation of transcription. 22 samples. 2 Cdk8 dsRNA, 4 CycC dsRNA, 4 Med12 dsRNA, 4 Med13 dsRNA, 8 control samples including 4 Luciferase (Luc) dsRNA and 4 GFP dsRNA

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Combinatorial Gene Essentiality and Pharmacological Profiling uncovers enhancer-mediated synthetic lethal interactions with Mediator Kinase [RNA-Seq]

Project description:Depletion of CDK8 and its paralogue CDK19, resulted in a global down regulation of mRNA expression, and hence we went to investigate the binding of RNA pol II by ChIP seq at the promoter and at the gene body in the DKO cells. To determine the consequence of loss of CDK8/19 in re-defining enhancers and to underpin the molecular mechanism that providing the preferential BET sensitivity for DKO, we performed ChIP sequencing for MED12, a reminiscent mediator kinase component, BRD4 and H3K27Ac. We identified that MED12 redefines the enhancer landscape in the absence of CDK8/19, recruit BRD4 at the cis regions and can be targeted using BET inhibitors

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