Abstract
Cellular senescence is a natural condition of irreversible cell cycle arrest and apoptotic resistance that occurs in cells exposed to various stress factors, such as replicative stress or overexpression of oncogenes. Unraveling the complex regulation of senescence in cells is essential to strengthen senescence-related therapeutic approaches in cancer, as cellular senescence plays a dual role in tumorigenesis, having both anti- and pro-tumorigenic effects. In our study we created a model of replicative cellular senescence, based on transcriptomic data, including an extra intermediate time-point prior to cells entering senescence, to elucidate the interplay of networks governing cellular senescence with networks involved in tumorigenesis. We reveal specific changes that occur in transcription factor activity at different timepoints before and after cells entering senescence and model the signaling networks that govern these changes.
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Data availability
The dataset supporting the conclusions of this article is available in the GEO repository, under the accession number GSE144703.
Code availability
The BioInfoMiner platform is available online at the website https://bioinfominer.com. DoRothEA, PROGENy and CARNIVAL are published tools, available online on the Saez lab Github page https://github.com/saezlab.
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Funding
This work was supported by the Research Funding Program: Thales “MAESTRO” co-financed by the European Union (European Social Fund) and Greek national funds through the Operational Program “Education and Lifelong Learning” of the National Strategic Reference Framework (NSRF) to NC and AC. This work has been also supported partly by EU H2020 MSCA ITN‐675448 (TRAINERS) and MSCA RISE‐734749 (INSPIRED) to AC. ΙΒ’s PhD thesis is supported by a scholarship from the State Scholarship Foundation in Greece (IKY) (Operational Program “Human Resources Development—Education and Lifelong Learning” Partnership Agreement (PA) 2014–2020).
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IB, NC and AC contributed to the study conception and design. Material preparation and data collection were performed by ML. Data analysis was performed by IB. The first draft of the manuscript was written by IB, review and editing were performed by IB, NC and AC. All authors read and approved the final manuscript.
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Aristotelis Chatziioannou is the founder and CEO of e-NIOS PC. Other authors declare that they have no conflict of interest.
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Binenbaum, I., Lefaki, M., Chondrogianni, N. et al. Bioinformatic framework for analysis of transcription factor changes as the molecular link between replicative cellular senescence signaling pathways and carcinogenesis. Biogerontology 21, 357–366 (2020). https://doi.org/10.1007/s10522-020-09866-y
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DOI: https://doi.org/10.1007/s10522-020-09866-y