SIRT1: a novel regulator in colorectal cancer

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.