Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province 110004, China.
Department of Health Management, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province 110004, China.
Biomed Pharmacother. 2024 Sep;178:117176. doi: 10.1016/j.biopha.2024.117176. Epub 2024 Jul 25.
The class-III histone deacetylase SIRT1 is the most extensively investigated sirtuin deacetylase. It is resistant to the broad deacetylase inhibitor trichostatin A and depends on oxidized nicotinamide adenine nucleotide (NAD). SIRT1 plays a crucial role in the tumorigenesis of numerous types of cancers, including colorectal cancer (CRC). Accumulating evidence indicates that SIRT1 is a therapeutic target for CRC; however, the function and underlying mechanism of SIRT1 in CRC still need to be elucidated. Herein, we provide a detailed and updated review to illustrate that SIRT1 regulates many processes that go awry in CRC cells, such as apoptosis, autophagy, proliferation, migration, invasion, metastasis, oxidative stress, resistance to chemo-radio therapy, immune evasion, and metabolic reprogramming. Moreover, we closely link our review to the clinical practice of CRC treatment, summarizing the mechanisms and prospects of SIRT1 inhibitors in CRC therapy. SIRT1 inhibitors as monotherapy in CRC or in combination with chemotherapy, radiotherapy, and immune therapies are comprehensively discussed. From epigenetic regulation to its potential therapeutic effect, we hope to offer novel insights and a comprehensive understanding of SIRT1's role in CRC.
III 类组蛋白去乙酰化酶 SIRT1 是研究最为广泛的去乙酰化酶 Sirtuin。它能抵抗广谱去乙酰化酶抑制剂 Trichostatin A，并且依赖于氧化型烟酰胺腺嘌呤二核苷酸（NAD）。SIRT1 在多种癌症的肿瘤发生中起着至关重要的作用，包括结直肠癌（CRC）。越来越多的证据表明 SIRT1 是 CRC 的治疗靶点；然而，SIRT1 在 CRC 中的功能和潜在机制仍需要阐明。本文详细地综述了 SIRT1 调控结直肠癌细胞中许多发生紊乱的过程，如细胞凋亡、自噬、增殖、迁移、侵袭、转移、氧化应激、化疗和放疗抵抗、免疫逃逸以及代谢重编程等。此外，我们将本文与 CRC 治疗的临床实践紧密联系起来，总结了 SIRT1 抑制剂在 CRC 治疗中的作用机制和前景。我们全面讨论了 SIRT1 抑制剂在 CRC 中的单药治疗或与化疗、放疗和免疫治疗联合应用。从表观遗传学调控到其潜在的治疗效果，我们希望为 SIRT1 在 CRC 中的作用提供新的见解和全面的认识。
