SIRT4 (Sirtuin 4)

Distinct integrated sirtuin scores thus capture subtype-specific metabolic/epigenetic states and provide robust RFS stratification across BC subtypes. These findings highlight sirtuins as integrators of longevity pathways and tumor metabolism, suggesting therapeutically exploitable vulnerabilities along NAD⁺-dependent regulatory axes.

The miR-15/16-SIRT4 axis represents a novel mechanism of post-transcriptional regulation in the DNA damage response and may serve as a therapeutic target to improve the efficacy of chemotherapy.

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.

This study successfully discovered nine GlnMgs that are associated with AS. These findings provide valuable insights into potential novel biomarkers for AS and offer prospects for monitoring disease progression.

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.

Our results revealed that AIL targeted mitophagy-loaded SIRT4 to regulate redox homeostasis, inducing mitochondrial dysfunction-mediated cell apoptosis and inhibiting gastric cancer growth. These findings provide strong evidence for the potential clinical use of AIL in gastric cancer treatment.

Preclinical studies have identified several sirtuin modulators-both inhibitors and activators-that alter tumor growth, sensitize cells to temozolomide, and regulate pathways such as JAK2/STAT3, NF-κB, and mitochondrial metabolism. Emerging evidence positions sirtuins as promising targets for glioma therapy. Future studies should evaluate sirtuin modulators in clinical trials and explore their potential for patient stratification and combined treatment strategies.

Therefore, SIRT3 is a key regulator involved in multiple mechanisms underlying DOX-induced cardiotoxicity. Several studies have shown the protective effects of SIRT3 against DOX-induced myocardial injury and have provided insights into its potential for future clinical applications.

However, 10 µM acetyl-CoA was neither able to enhance H3K27 acetylation, nor to promote stem cell-like properties, while forced expression of SIRT4 in α2δ1+ cells resulted in retardation of tumor growth in vivo. Thus, SIRT4 serves as an oncogene to promote stemness and invasiveness by controlling the production of acetyl-CoA, linking α2δ1-mediated calcium signaling to SIRT4-mediated epigenetic reprogramming of HCC TICs which hold significant potential for the development of novel therapeutic strategies targeting TICs, and the dual roles of SIRT4 in HCC might be dependent on the production levels of acetyl-CoA.

Interestingly, both SIRT4 and deacetylated mimetic of ENO1-K358 can increase the lactylation of histones at multiple sites including H3K9 and H3K18 sites, which resulted in epigenetic reprogramming to directly activate a variety of pathways that are essential for stemness. Hence, the study links α2δ1-mediated calcium signaling to SIRT4-mediated histone lactylation epigenetic reprogramming in promoting the stem cell-like properties of pancreatic cancer, which holds significant potential for the development of novel therapeutic strategies by targeting TICs of pancreatic cancer.

These data were associated with increased SIRT4 expression levels (p < 0.01) and the activation of AMPK signaling (p < 0.01). Overall, the results, by supporting the importance of nutritional factors in CRC management, highlight l-carnitine and acetyl-l-carnitine as promising agents to target CRC metabolic vulnerabilities.

In summary, SIRT4 inhibits the progression and immune escape of BCa, indicating its potential as a novel biomarker and immune checkpoint for immunotherapy.