DOI: 10.17798/bitlisfen.1896315 ISSN: 2147-3129

An Integrative In Silico Analysis of The Per2–Tp53 Axis In Circadian–Oncogenic Regulation In Breast Carcinogenesis

İlkay Civelek
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Circadian clock dysfunction, often associated with shift work, is classified as a probable carcinogen by the International Agency for Research on Cancer (IARC). Epidemiological studies suggest a possible link between shift work and breast cancer, but how it specifically connects on the molecular level has not been well elucidated. To address this, an in silico framework is presented, to the best of the author's knowledge, for exploring possible connections between circadian factors and cancer and for generating testable hypotheses for further study. All data is derived from publicly available data via Ensembl/BioMart (version 110) and STRING-DB (version 12.0) databases for a 14-gene panel based on PPI networks. TP53 and PER2 were found to be crucial nodes within the interaction networks, with PER2 showing a non-random centrality with Degree = 8 (empirical p = 0.0034, n = 10,000 permutations). Based upon this observation, an analytical framework is proposed upon which there may be a potential dual vulnerability (‘Double Failure’) within circadian clock function as well as oncogenesis. This paper is based on an original ‘in silico’ study to provide functional insights based on integrated genomic data.

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