Deciphering the role of sirtuins in cancer immunoregulation through molecular cross-talk and docking-based interaction.

The Sirtuin family (SIRT1-SIRT7) of NAD+-dependent histone deacetylases (HDACs) serves as a fundamental regulator of cellular homeostasis, governing protein acylation, metabolic flux, and genomic integrity. Cancer cells often bypass the pre-defined cellular disciplines and promote metastasis, angiogenesis in the microenvironment for self-survival. This review thoroughly focuses on deciphering the impact of Sirtuins in oncology, specifically their molecular involvement in oxidative stress, redox signaling, and tumor-associated angiogenesis. We evaluate the distinct biological footprints of nuclear, mitochondrial, and cytoplasmic Sirtuins, illustrating their context-dependent roles as both tumor suppressors and oncogenic drivers. Key interactions with transcription factors such as p53, FOXO, and HIF-1α are examined to understand Sirtuin-mediated pathway modulation in various cancer progression including breast, oral, and liver cancers. Crucially, we reviewed the modulatory role of Sirtuins in FOXP3 expression and Treg differentiation, providing insight into their contribution to tumor immunosuppression. By integrating network-based analysis, we identified miR-34a as a central regulator and validated the miRNA-Transcription Factor-Sirtuin axis as a viable framework for cancer therapeutic targeting. Furthermore, we established molecular docking between SIRT1 and HIF-1α to clarify the structural basis for deacetylation-mediated control of hypoxia signaling. These findings emphasize the potential of Sirtuins as strategic targets for precision oncology and advanced anti-cancer therapeutics.