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    Oncoproteins E6/E7 of the human papillomavirus types 16 & 18 synergize in modulating oncogenes and tumor suppressor proteins in colorectal cancer

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    37395a24-84e4-4ebe-8bcb-747a9c93e649.pdf (1.715Mb)
    Date
    2025
    Author
    Fernandes, Queenie
    Therachiyil, Lubna
    Younis, Shahd M
    Dermime, Said
    Al Moustafa, Ala-Eddin
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    Abstract
    Objective Our study presents a novel analysis of the oncogenes and tumor suppressor proteins directly modulated by E6/E7 of high-risk HPV types 16 and 18, in colorectal cancer (CRC). Methods HCT 116 (KRAS mutant) & HT-29 (TP53 mutant) cell models of CRC were transduced with E6/E7 of HPV16 and HPV18, individually and in combination. Further, we utilized a liquid chromatography mass spectrometry (LC-MS/MS) approach to analyze and compare the proteomes of both CRC cell models. Results We generated six stably transduced cell lines. Our data revealed a significantly higher, HPV-induced modulation of oncogenes and tumor suppressor proteins in the TP53 mutant model, as compared to the KRAS mutant model (p ≤ 0.01). Less than 1% of the genes were commonly modulated by HPV, between both models. We also report that HT-29 cells, expressing E6/E7 of both HPV types, significantly reduced the suppression of oncogenes as compared to cells expressing E6/E7 of either HPV types individually (p-value ≤0.00001). Conclusion Our data imply that HPV coinfections leads to the sustenance of a pro-oncogenic environment in CRC. HPV modulates different oncogenes/tumor suppressor proteins in CRC of varying mutational backgrounds, thus highlighting the importance of personalized therapies for such diseases with mutational heterogeneity.
    DOI/handle
    http://dx.doi.org/10.1080/14789450.2025.2455104
    http://hdl.handle.net/10576/63429
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    • Biomedical Research Center Research [‎786‎ items ]
    • Medicine Research [‎1753‎ items ]
    • Public Health [‎484‎ items ]

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