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Review
. 2024 Jun 14:14:1384928.
doi: 10.3389/fonc.2024.1384928. eCollection 2024.

The dual role of sirtuins in cancer: biological functions and implications

Lu Yu #  1 , Yanjiao Li #  2 , Siyuan Song #  3 , Yalin Zhang #  4   5 , Yiping Wang  5 , Hailian Wang  6 , Zhengteng Yang  7 , Yi Wang  5   6
Affiliations
Review

The dual role of sirtuins in cancer: biological functions and implications

Lu Yu et al. Front Oncol. .

Abstract

Sirtuins are pivotal in orchestrating numerous cellular pathways, critically influencing cell metabolism, DNA repair, aging processes, and oxidative stress. In recent years, the involvement of sirtuins in tumor biology has garnered substantial attention, with a growing body of evidence underscoring their regulatory roles in various aberrant cellular processes within tumor environments. This article delves into the sirtuin family and its biological functions, shedding light on their dual roles-either as promoters or inhibitors-in various cancers including oral, breast, hepatocellular, lung, and gastric cancers. It further explores potential anti-tumor agents targeting sirtuins, unraveling the complex interplay between sirtuins, miRNAs, and chemotherapeutic drugs. The dual roles of sirtuins in cancer biology reflect the complexity of targeting these enzymes but also highlight the immense therapeutic potential. These advancements hold significant promise for enhancing clinical outcomes, marking a pivotal step forward in the ongoing battle against cancer.

Keywords: cancer therapy; histone deacetylase; metabolic functions; sirtuins; tumor.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The Domain of Sirtuins.
Figure 2
Figure 2
The metabolic modulation by SIRTs in cancer cells. SIRT3, SIRT4, and SIRT6 significantly impact cancer cell metabolism by downregulating key pathways crucial for tumor growth. These sirtuins suppress HIF-1α and IRP1 target genes, affecting glycolytic processes by inhibiting genes such as PDK1, PFK, and Pfkm, alongside Glut1, which is vital for glucose transport. They also regulate iron metabolism by modulating the expression of DMT1 and other bivalent metal transporters, as well as ferritin and the transferrin receptor. The influence extends to MYC target genes, including ribosomal proteins Rpl3, Rpl6, Rpl23, and Rps15a, thereby reducing the metabolic rate encompassing aerobic glycolysis, the tricarboxylic acid (TCA) cycle, and glutamine decomposition. Additionally, the activation of the mTORC1 pathway leads to CREB2 degradation, which results in decreased SIRT4 expression, illustrating a comprehensive mechanism by which these sirtuins suppress metabolic pathways to hinder cancer progression.
Figure 3
Figure 3
SIRTuins’ involvement in DNA repair mechanisms. SIRT6 plays a crucial role in the base excision repair (BER) pathway by interacting with key components such as Myosin heavy chain (MYH), Apurinic/Apyrimidinic endonuclease 1 (APE1), and the Rad 9-RAD 1-Hus 1 (9–1–1) complex. SIRT1 enhances the DNA repair process by promoting the deacetylation of APE1 and Thymine DNA glycosylase (TDG). In the context of double-strand break (DSB) repair, SIRT6 boosts the activity of ADP-Ribose polymerase 1 (PARP1) and facilitates the deacetylation of CtIP. It also interacts with the DNA-dependent protein kinase Catalytic subunit (DNA-PKcs) and Sucrose Nonfermenter2 Homolog (SNF2H), playing a vital role in responding to DNA damage. Moreover, SIRT1 is instrumental in augmenting DNA repair by promoting the acetylation of Nijmegen breakage syndrome 1 (NBS1), Ku70, Bax, and Werner syndrome protein (WRN). In the nucleotide excision repair (NER) pathway, SIRT1 increases the efficacy of DNA repair by enhancing the interaction between Rad3-related phosphorylation of Xeroderma Pigmentosum (XPA) and Replication protein A32 (RPA32), showcasing the comprehensive involvement of SIRTuins in maintaining genomic stability through various DNA repair mechanisms.
Figure 4
Figure 4
Sirtuins’ role in cell survival and stress response. Sirtuins orchestrate cell fate under various stress conditions by modulating key apoptotic and survival pathways. SIRT1 plays a pivotal role in cell survival by interacting with critical regulators such as P53, FOXO, and NF-κB, while SIRT2 and SIRT6 similarly influence NF-κB signaling. SIRT3, on the other hand, contributes to apoptosis regulation by targeting P53 and FOXO3a. Through these interactions, sirtuins serve as vital mediators of cellular stress response, ensuring cell survival by fine-tuning the balance.
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References

    1. Garcia-Martinez L, Zhang Y, Nakata Y, Chan HL, Morey L. Epigenetic mechanisms in breast cancer therapy and resistance. Nat Commun. (2021) 12:1786. doi: 10.1038/s41467-021-22024-3 - DOI - PMC - PubMed
    1. Hogg SJ, Beavis PA, Dawson MA, Johnstone RW. Targeting the epigenetic regulation of antitumour immunity. Nat Rev Drug Discovery. (2020) 19:776–800. doi: 10.1038/s41573-020-0077-5 - DOI - PubMed
    1. Miranda Furtado CL, Dos Santos Luciano MC, Silva Santos RD, Furtado GP, Moraes MO, Pessoa C. Epidrugs: targeting epigenetic marks in cancer treatment. Epigenetics. (2019) 14:1164–76. doi: 10.1080/15592294.2019.1640546 - DOI - PMC - PubMed
    1. Audia JE, Campbell RM. Histone modifications and cancer. Cold Spring Harb Perspect Biol. (2016) 8:a019521. doi: 10.1101/cshperspect.a019521 - DOI - PMC - PubMed
    1. Zaib S, Rana N, Khan I. Histone modifications and their role in epigenetics of cancer. Curr Med Chem. (2022) 29:2399–411. doi: 10.2174/0929867328666211108105214 - DOI - PubMed

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by the National Natural Science Foundation of China (81802504), grants from the Sichuan Science and Technology Department 2021YFS0380 and 2023YFH0010).

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