SIRT2 (Sirtuin 2)

The in vivo validation suggested that SIRT2 played a regulatory role in FZD1 expression and Wnt/β-catenin pathway, thereby hindering the growth and metastasis of the orthotopic tongue cancer xenograft model. SIRT2 inhibits the transcriptional expression of FZD1 through H3K27 deacetylation to block the Wnt/β-catenin pathway, consequently suppressing the growth and metastasis of tongue cancer.

SIRT6 overexpression was linked to favorable prognosis in esophageal carcinoma and sarcoma, while unfavorable outcomes were observed in hepatocellular carcinoma and cholangiocarcinoma. SIRT7 upregulation was significantly associated with reduced survival in esophageal, liver, and uterine cancers, but surprisingly correlated with improved outcomes in urothelial carcinoma and cervical squamous cell carcinoma.ConclusionsTogether, this multi-omics analysis reveals the correlation and prognostic values of sirtuins across multiple types of human cancers and suggests that sirtuins may serve as promising biomarkers for different cancers.

SIRT2 is upregulated in GC tissues and is associated with poor prognosis. It may serve as a promising biomarker for predicting GC progression and evaluating patient outcomes.

In contrast, SIRT1 expression was not significantly associated with these parameters. Both SIRT1 and SIRT2 showed a statistically significant relationship with K-RAS mutations, highlighting their potential roles in the molecular pathology of colorectal cancer.

Notably, Bushen Huoxue Acupuncture outperformed non-acupoint acupuncture in enhancing cognitive function and reducing inflammation. Our findings indicate that Bushen Huoxue Acupuncture alleviates cognitive deficits and neuroinflammation by suppressing the SIRT2-mediated RTN4B/BACE1 pathway, highlighting acupuncture as a promising therapy for neurodegenerative diseases.

SIRT2 is posited as a pathogenic gene for HCC. It may facilitate the growth and invasion of HCC via multiple mechanisms, including Cuproptosis, tumor microenvironment modulation, metabolic pathway alteration, and immune checkpoint activation. SIRT2 presents as a potential biomarker for HCC and may serve as a novel therapeutic target for its treatment.

The data from the CTRP database and the Cell Counting Kit-8 (CCK-8) experiment suggested that SIRT1 increased the sensitivity of B-ALL cell lines to vincristine. In vitro experiments demonstrated that SIRT1 inhibits invasion activity in B-ALL cell lines (NALM6 and REH). SIRT1 represents a potential prognostic biomarker and therapeutic target in childhood B-ALL.

Furthermore, molecular docking analysis revealed favorable binding interactions between the compounds and key amino acids of the G6PD, reinforcing their potential as a direct enzyme inhibitors. These findings highlight the pivotal role of G6PD in gliomas under hypoxic conditions and support its inhibition as a promising therapeutic strategy.

The histopathological assessment of myocardial damage provided supportive evidence for the biochemical results obtained. In conclusion, the BB extract (80.0 mg/kg) can attenuate the DOX-induced oxidative stress, and it has the potential to be developed as an adjunct against DOX-induced cardiotoxicity in cancer patients who undergo anthracycline chemotherapy.

Mechanistically, circSMPD4 physically combines LDHA to reduce its acetylation levels via SIRT2-dependent deacetylation and thus preventing its degradation from chaperone-mediated autophagy-lysosome pathway. These findings unveil an oncogenic circRNA and elucidate a novel regulatory mechanism by which tumor cell metabolic reprogramming facilitates tumor immune evasion and tumor progression.

These integrated results, spanning virtual screening to in vivo validation, identify Compound 7 as a promising lead compound. The study establishes a solid foundation for developing novel SIRT2 inhibitors as both chemical probes and potential therapeutics for SIRT2-driven NSCLC.

Last, a combination strategy using SIRT2 inhibitor 2-cyano-3-[5-(2,5-dichlorophenyl)-2-furanyl]-N-5-quinolinyl-2-propenamide (AGK2) and anti-programmed cell death protein-1 (PD-1) therapy enhanced immune response, making tumors susceptible to immunotherapy and driving substantial tumor regression in vivo. Our study uncovers a role of SIRT2 in reprogramming TME and underscores the potential of targeting SIRT2 to sensitize CRC to immunotherapy.