Comprehensive analysis of the transcriptional profile of the Mediator complex across human cancer types

Isabella Syring; Niklas Klümper; Anne Offermann; Martin Braun; Mario Deng; Diana Boehm; Angela Queisser; Anne von Mässenhausen; Johannes Brägelmann; Wenzel Vogel; Doris Schmidt; Michael Majores; Anne Schindler; Glen Kristiansen; Stefan C. Müller; Jörg Ellinger; Zaki Shaikhibrahim; Sven Perner

doi:10.18632/oncotarget.8469

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Research Papers: Pathology:

Comprehensive analysis of the transcriptional profile of the Mediator complex across human cancer types

Isabella Syring, Niklas Klümper, Anne Offermann, Martin Braun, Mario Deng, Diana Boehm, Angela Queisser, Anne von Mässenhausen, Johannes Brägelmann, Wenzel Vogel, Doris Schmidt, Michael Majores, Anne Schindler, Glen Kristiansen, Stefan C. Müller, Jörg Ellinger, Zaki Shaikhibrahim and Sven Perner _

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Oncotarget. 2016; 7:23043-23055. https://doi.org/10.18632/oncotarget.8469

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Abstract

Isabella Syring1,2,3,4,*, Niklas Klümper,5,*, Anne Offermann5, Martin Braun1,2,3, Mario Deng5, Diana Boehm5, Angela Queisser5, Anne von Mässenhausen5, Johannes Brägelmann1,2,3,6, Wenzel Vogel5, Doris Schmidt3,4, Michael Majores2, Anne Schindler2, Glen Kristiansen2, Stefan C. Müller3,4, Jörg Ellinger3,4, David Adler5 and Sven Perner5

1 Section for Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany

2 Institute of Pathology, University Hospital of Bonn, Bonn, Germany

3 Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany

4 Clinic for Urology and Pediatric Urology, University Hospital of Bonn, Bonn, Germany

5 Pathology of the University Hospital of Lübeck and Leibniz Research Center Borstel, Lübeck and Borstel, Germany

6 Department of Oncology, Hematology and Rheumatology, University Hospital Bonn, Bonn, Germany

* These authors have contributed equally to this work

Correspondence to:

Sven Perner, email:

Keywords: transcriptional profile, Mediator complex, cancer, oncomine, MED8, Pathology Section

Received: June 26, 2015 Accepted: March 04, 2016 Published: March 30, 2016

Abstract

The Mediator complex is a key regulator of gene transcription and several studies demonstrated altered expressions of particular subunits in diverse human diseases, especially cancer. However a systematic study deciphering the transcriptional expression of the Mediator across different cancer entities is still lacking.

We therefore performed a comprehensive in silico cancer vs. benign analysis of the Mediator complex subunits (MEDs) for 20 tumor entities using Oncomine datasets. The transcriptional expression profiles across almost all cancer entities showed differentially expressed MEDs as compared to benign tissue. Differential expression of MED8 in renal cell carcinoma (RCC) and MED12 in lung cancer (LCa) were validated and further investigated by immunohistochemical staining on tissue microarrays containing large numbers of specimen. MED8 in clear cell RCC (ccRCC) associated with shorter survival and advanced TNM stage and showed higher expression in metastatic than primary tumors. In vitro, siRNA mediated MED8 knockdown significantly impaired proliferation and motility in ccRCC cell lines, hinting at a role for MED8 to serve as a novel therapeutic target in ccRCC. Taken together, our Mediator complex transcriptome proved to be a valid tool for identifying cancer-related shifts in Mediator complex composition, revealing that MEDs do exhibit cancer specific transcriptional expression profiles.

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Research Papers: Pathology:

Comprehensive analysis of the transcriptional profile of the Mediator complex across human cancer types

Abstract