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Updated: Jul 13, 2025

Yeast As a Chassis for Developing Functional Assays to Study Human P53
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Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

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

Irene Lo Cigno1, Federica Calati1, Carlo Girone1

  • 1Virology Unit, Department of Translational Medicine, Eastern Piedmont University, Novara, Italy.

British Journal of Cancer
|October 14, 2023
PubMed
Abstract

Insights

Targeting SIRT1 (silent mating type information regulation 2 homolog 1) restores p53 function and inhibits human papillomavirus (HPV)-driven cancers. This precision medicine approach shows promise for treating HPV-associated malignancies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Precision Medicine

Background:

  • Human papillomavirus (HPV) infection is a major cause of various cancers.
  • SIRT1 (silent mating type information regulation 2 homolog 1) plays a role in HPV-driven oncogenesis.
  • Restoring functional p53 is a potential strategy for cancer treatment.

Purpose of the Study:

  • To evaluate the efficacy of targeting a SIRT1-dependent pathway for cancer therapy.
  • To investigate the role of SIRT1 inhibition in restoring p53 function in HPV-transformed cells.
  • To assess the anti-cancer action of a precision medicine approach involving SIRT1 inhibition.

Main Methods:

  • Utilized the SIRT1 inhibitor EX527 (Selisistat) and genetic silencing of SIRT1.
  • Tested effects on various HPV-positive (HPV+) cancer cell lines and an HPV16-induced mouse model.
  • Assessed p53 acetylation, cell cycle arrest, clonogenicity, and sensitivity to chemotherapeutic agents.

Main Results:

  • SIRT1 inhibition restored transcriptionally active, K382-acetylated p53 specifically in HPV+ cells.
  • This restoration led to G0/G1 cell cycle arrest and inhibited clonogenicity in HPV+ cells.
  • EX527 treatment enhanced HPV+ cell sensitivity to genotoxic agents and showed efficacy in an in vivo mouse model.

Conclusions:

  • SIRT1 is essential for HPV-driven oncogenesis.
  • Targeting SIRT1 represents a potential precision medicine strategy for HPV-associated cancers.
  • Findings have direct translational implications for treating HPV-driven malignancies.

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