SIRT1 is an actionable target to restore p53 function in HPV-associated cancer therapy.


Journal

British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635

Informations de publication

Date de publication:
Nov 2023
Historique:
received: 05 06 2023
accepted: 04 10 2023
revised: 26 09 2023
pmc-release: 14 10 2024
medline: 27 11 2023
pubmed: 15 10 2023
entrez: 14 10 2023
Statut: ppublish

Résumé

Our aim was to evaluate the efficacy and anti-cancer action of a precision medicine approach involving a novel SIRT1-dependent pathway that, when disrupted, leads to the restoration of a functional p53 in human papillomavirus (HPV)-transformed cells. The anticancer potential of inhibiting SIRT1 was evaluated by examining the effects of the specific SIRT1 inhibitor EX527 (also known as Selisistat) or genetic silencing, either individually or in conjunction with standard chemotherapeutic agents, on a range of HPV We show that SIRT1 inhibition restores a transcriptionally active K382-acetylated p53 in HPV Our findings uncover an essential role of SIRT1 in HPV-driven oncogenesis, which may have direct translational implications for the treatment of this type of cancer.

Sections du résumé

BACKGROUND BACKGROUND
Our aim was to evaluate the efficacy and anti-cancer action of a precision medicine approach involving a novel SIRT1-dependent pathway that, when disrupted, leads to the restoration of a functional p53 in human papillomavirus (HPV)-transformed cells.
METHODS METHODS
The anticancer potential of inhibiting SIRT1 was evaluated by examining the effects of the specific SIRT1 inhibitor EX527 (also known as Selisistat) or genetic silencing, either individually or in conjunction with standard chemotherapeutic agents, on a range of HPV
RESULTS RESULTS
We show that SIRT1 inhibition restores a transcriptionally active K382-acetylated p53 in HPV
CONCLUSIONS CONCLUSIONS
Our findings uncover an essential role of SIRT1 in HPV-driven oncogenesis, which may have direct translational implications for the treatment of this type of cancer.

Identifiants

pubmed: 37838812
doi: 10.1038/s41416-023-02465-x
pii: 10.1038/s41416-023-02465-x
pmc: PMC10667542
doi:

Substances chimiques

Tumor Suppressor Protein p53 0
Sirtuin 1 EC 3.5.1.-
Cyclin-Dependent Kinase Inhibitor p21 0
Oncogene Proteins, Viral 0
SIRT1 protein, human EC 3.5.1.-

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1863-1874

Informations de copyright

© 2023. The Author(s), under exclusive licence to Springer Nature Limited.

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Auteurs

Irene Lo Cigno (I)

Virology Unit, Department of Translational Medicine, Eastern Piedmont University, Novara, Italy.

Federica Calati (F)

Virology Unit, Department of Translational Medicine, Eastern Piedmont University, Novara, Italy.

Carlo Girone (C)

Virology Unit, Department of Translational Medicine, Eastern Piedmont University, Novara, Italy.

Cinzia Borgogna (C)

Virology Unit, Department of Translational Medicine, Eastern Piedmont University, Novara, Italy.

Aldo Venuti (A)

HPV Unit, UOSD Tumor Immunology and Immunotherapy, IRCCS Regina Elena National Cancer Institute, Rome, Italy.

Renzo Boldorini (R)

Pathology Unit, Department of Health Sciences, Eastern Piedmont University, Novara, Italy.

Marisa Gariglio (M)

Virology Unit, Department of Translational Medicine, Eastern Piedmont University, Novara, Italy. marisa.gariglio@med.uniupo.it.

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Classifications MeSH