Cargando…
Oncogenic B-Myb Is Associated With Deregulation of the DREAM-Mediated Cell Cycle Gene Expression Program in High Grade Serous Ovarian Carcinoma Clinical Tumor Samples
Cell cycle control drives cancer progression and treatment response in high grade serous ovarian carcinoma (HGSOC). MYBL2 (encoding B-Myb), an oncogene with prognostic significance in several cancers, is highly expressed in most HGSOC cases; however, the clinical significance of B-Myb in this diseas...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969987/ https://www.ncbi.nlm.nih.gov/pubmed/33747961 http://dx.doi.org/10.3389/fonc.2021.637193 |
_version_ | 1783666344411004928 |
---|---|
author | Iness, Audra N. Rubinsak, Lisa Meas, Steven J. Chaoul, Jessica Sayeed, Sadia Pillappa, Raghavendra Temkin, Sarah M. Dozmorov, Mikhail G. Litovchick, Larisa |
author_facet | Iness, Audra N. Rubinsak, Lisa Meas, Steven J. Chaoul, Jessica Sayeed, Sadia Pillappa, Raghavendra Temkin, Sarah M. Dozmorov, Mikhail G. Litovchick, Larisa |
author_sort | Iness, Audra N. |
collection | PubMed |
description | Cell cycle control drives cancer progression and treatment response in high grade serous ovarian carcinoma (HGSOC). MYBL2 (encoding B-Myb), an oncogene with prognostic significance in several cancers, is highly expressed in most HGSOC cases; however, the clinical significance of B-Myb in this disease has not been well-characterized. B-Myb is associated with cell proliferation through formation of the MMB (Myb and MuvB core) protein complex required for transcription of mitotic genes. High B-Myb expression disrupts the formation of another transcriptional cell cycle regulatory complex involving the MuvB core, DREAM (DP, RB-like, E2F, and MuvB), in human cell lines. DREAM coordinates cell cycle dependent gene expression by repressing over 800 cell cycle genes in G0/G1. Here, we take a bioinformatics approach to further evaluate the effect of B-Myb expression on DREAM target genes in HGSOC and validate our cellular model with clinical specimens. We show that MYBL2 is highly expressed in HGSOC and correlates with expression of DREAM and MMB target genes in both The Cancer Genome Atlas (TCGA) as well as independent analyses of HGSOC primary tumors (N = 52). High B-Myb expression was also associated with poor overall survival in the TCGA cohort and analysis by a DREAM target gene expression signature yielded a negative impact on survival. Together, our data support the conclusion that high expression of MYBL2 is associated with deregulation of DREAM/MMB-mediated cell cycle gene expression programs in HGSOC and may serve as a prognostic factor independent of its cell cycle role. This provides rationale for further, larger scale studies aimed to determine the clinical predictive value of the B-Myb gene expression signature for treatment response as well as patient outcomes. |
format | Online Article Text |
id | pubmed-7969987 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79699872021-03-19 Oncogenic B-Myb Is Associated With Deregulation of the DREAM-Mediated Cell Cycle Gene Expression Program in High Grade Serous Ovarian Carcinoma Clinical Tumor Samples Iness, Audra N. Rubinsak, Lisa Meas, Steven J. Chaoul, Jessica Sayeed, Sadia Pillappa, Raghavendra Temkin, Sarah M. Dozmorov, Mikhail G. Litovchick, Larisa Front Oncol Oncology Cell cycle control drives cancer progression and treatment response in high grade serous ovarian carcinoma (HGSOC). MYBL2 (encoding B-Myb), an oncogene with prognostic significance in several cancers, is highly expressed in most HGSOC cases; however, the clinical significance of B-Myb in this disease has not been well-characterized. B-Myb is associated with cell proliferation through formation of the MMB (Myb and MuvB core) protein complex required for transcription of mitotic genes. High B-Myb expression disrupts the formation of another transcriptional cell cycle regulatory complex involving the MuvB core, DREAM (DP, RB-like, E2F, and MuvB), in human cell lines. DREAM coordinates cell cycle dependent gene expression by repressing over 800 cell cycle genes in G0/G1. Here, we take a bioinformatics approach to further evaluate the effect of B-Myb expression on DREAM target genes in HGSOC and validate our cellular model with clinical specimens. We show that MYBL2 is highly expressed in HGSOC and correlates with expression of DREAM and MMB target genes in both The Cancer Genome Atlas (TCGA) as well as independent analyses of HGSOC primary tumors (N = 52). High B-Myb expression was also associated with poor overall survival in the TCGA cohort and analysis by a DREAM target gene expression signature yielded a negative impact on survival. Together, our data support the conclusion that high expression of MYBL2 is associated with deregulation of DREAM/MMB-mediated cell cycle gene expression programs in HGSOC and may serve as a prognostic factor independent of its cell cycle role. This provides rationale for further, larger scale studies aimed to determine the clinical predictive value of the B-Myb gene expression signature for treatment response as well as patient outcomes. Frontiers Media S.A. 2021-03-04 /pmc/articles/PMC7969987/ /pubmed/33747961 http://dx.doi.org/10.3389/fonc.2021.637193 Text en Copyright © 2021 Iness, Rubinsak, Meas, Chaoul, Sayeed, Pillappa, Temkin, Dozmorov and Litovchick. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Iness, Audra N. Rubinsak, Lisa Meas, Steven J. Chaoul, Jessica Sayeed, Sadia Pillappa, Raghavendra Temkin, Sarah M. Dozmorov, Mikhail G. Litovchick, Larisa Oncogenic B-Myb Is Associated With Deregulation of the DREAM-Mediated Cell Cycle Gene Expression Program in High Grade Serous Ovarian Carcinoma Clinical Tumor Samples |
title | Oncogenic B-Myb Is Associated With Deregulation of the DREAM-Mediated Cell Cycle Gene Expression Program in High Grade Serous Ovarian Carcinoma Clinical Tumor Samples |
title_full | Oncogenic B-Myb Is Associated With Deregulation of the DREAM-Mediated Cell Cycle Gene Expression Program in High Grade Serous Ovarian Carcinoma Clinical Tumor Samples |
title_fullStr | Oncogenic B-Myb Is Associated With Deregulation of the DREAM-Mediated Cell Cycle Gene Expression Program in High Grade Serous Ovarian Carcinoma Clinical Tumor Samples |
title_full_unstemmed | Oncogenic B-Myb Is Associated With Deregulation of the DREAM-Mediated Cell Cycle Gene Expression Program in High Grade Serous Ovarian Carcinoma Clinical Tumor Samples |
title_short | Oncogenic B-Myb Is Associated With Deregulation of the DREAM-Mediated Cell Cycle Gene Expression Program in High Grade Serous Ovarian Carcinoma Clinical Tumor Samples |
title_sort | oncogenic b-myb is associated with deregulation of the dream-mediated cell cycle gene expression program in high grade serous ovarian carcinoma clinical tumor samples |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969987/ https://www.ncbi.nlm.nih.gov/pubmed/33747961 http://dx.doi.org/10.3389/fonc.2021.637193 |
work_keys_str_mv | AT inessaudran oncogenicbmybisassociatedwithderegulationofthedreammediatedcellcyclegeneexpressionprograminhighgradeserousovariancarcinomaclinicaltumorsamples AT rubinsaklisa oncogenicbmybisassociatedwithderegulationofthedreammediatedcellcyclegeneexpressionprograminhighgradeserousovariancarcinomaclinicaltumorsamples AT measstevenj oncogenicbmybisassociatedwithderegulationofthedreammediatedcellcyclegeneexpressionprograminhighgradeserousovariancarcinomaclinicaltumorsamples AT chaouljessica oncogenicbmybisassociatedwithderegulationofthedreammediatedcellcyclegeneexpressionprograminhighgradeserousovariancarcinomaclinicaltumorsamples AT sayeedsadia oncogenicbmybisassociatedwithderegulationofthedreammediatedcellcyclegeneexpressionprograminhighgradeserousovariancarcinomaclinicaltumorsamples AT pillapparaghavendra oncogenicbmybisassociatedwithderegulationofthedreammediatedcellcyclegeneexpressionprograminhighgradeserousovariancarcinomaclinicaltumorsamples AT temkinsarahm oncogenicbmybisassociatedwithderegulationofthedreammediatedcellcyclegeneexpressionprograminhighgradeserousovariancarcinomaclinicaltumorsamples AT dozmorovmikhailg oncogenicbmybisassociatedwithderegulationofthedreammediatedcellcyclegeneexpressionprograminhighgradeserousovariancarcinomaclinicaltumorsamples AT litovchicklarisa oncogenicbmybisassociatedwithderegulationofthedreammediatedcellcyclegeneexpressionprograminhighgradeserousovariancarcinomaclinicaltumorsamples |