Hyperactivation of p53 using CRISPRa kills human papillomavirus-driven cervical cancer cells
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Lai, Alan J
McMillan, Nigel AJ
Idris, Adi
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Abstract
Clinical and pre-clinical work for a number of cancer types has demonstrated relatively positive outcomes and effective tumour regression when the level and function of p53, a well-established tumour suppressor, is restored. Human papillomavirus (HPV)-driven cancers encode the E6 oncoprotein, which leads to p53 degradation, to allow the carcinogenic process to proceed. Indeed, there have been several attempts to revive p53 function in HPV-driven cancers by both pharmacological and genetic means to increase p53 bioavailability. Here, we employed a CRISPR activation (CRISPRa) approach to overcome HPV-mediated silencing of p53 by hyperexpressing the p53 gene promoter. Our data show that CRISPRa-mediated hyperexpression of p53 leads to HPV+ cervical cancer cell killing and the reduction of cell proliferation. This proof-of-concept data suggest that increasing p53 bioavailability may potentially be a promising therapeutic approach for the treatment of HPV-driven cancers.
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Virus Genes
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© 2022 Springer Netherlands. This is an electronic version of an article published in Virus Genes 2022. Virus Genes is available online at: http://link.springer.com/ with the open URL of your article.
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Biological sciences
Health sciences
Virology
Oncology and carcinogenesis
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
Virology
p53
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Idres, YM; Lai, AJ; McMillan, NAJ; Idris, A, Hyperactivation of p53 using CRISPRa kills human papillomavirus-driven cervical cancer cells, Virus Genes, 2022