Targeting sirtuins for cancer therapy: epigenetics modifications and beyond

Theranostics, Journal Year: 2024, Volume and Issue: 14(17), P. 6726 - 6767

Published: Jan. 1, 2024

Sirtuins (SIRTs) are well-known as nicotinic adenine dinucleotide

Language: Английский

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SIRT7 affects the proliferation and apoptosis of papillary thyroid cancer cells by desuccinylation of LATS1

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 6, 2025

Papillary thyroid cancer (PTC) is one of the malignant tumors with rapidly increasing morbidity and mortality. Sirtuin 7 (SIRT7) a desuccinylase that involved in tumorigenesis. The activation large tumor suppressor 1 (LATS1) can effectively suppress tumorigenesis multiple be affected by SIRT7. This study aimed to explore role mechanism SIRT7 PTC progression. RNA protein levels were detected quantitative real-time PCR (qPCR) western blot, respectively. Cell proliferation was measured cell counting kit-8 colony formation. apoptosis cells analyzed flow cytometry Live/dead staining. interaction between proteins co-immunoprecipitation. results showed highly expressed tissues cells. Functional studies knockdown inhibited induced Mechanistically, could directly interact LATS1 reduce stability protein. Later, rescue experiments suggested silencing reversed effect on growth apoptosis. In addition, promoted vivo. Taken together, promotes succinylation enhance stability, thus inhibiting progression PTC. Therefore, may become novel potential therapeutic targets for

Language: Английский

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Aging insights from heterochronic parabiosis models

npj Aging, Journal Year: 2024, Volume and Issue: 10(1)

Published: Aug. 17, 2024

Heterochronic parabiosis consists of surgically connecting the circulatory systems a young and an old animal. This technique serves as model to study circulating factors that accelerate aging in organisms exposed blood or induce rejuvenation blood. Despite promising results, exact cellular molecular mechanisms remain unclear, so this aims explore elucidate them more detail.

Language: Английский

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Implication of protein post translational modifications in gastric cancer

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 4, 2025

Gastric cancer (GC) is one of the most common and highly lethal malignant tumors worldwide, its occurrence development are regulated by multiple molecular mechanisms. Post-translational modifications (PTM) forms include ubiquitylation, phosphorylation, acetylation methylation. Emerging research has highlighted lactylation glycosylation. The diverse realm PTM crosstalk linked to many critical signaling events involved in neoplastic transformation, carcinogenesis metastasis. This review provides a comprehensive overview impact on progression GC. Specifically, aberrant have been shown alter proliferation, migration, invasion capabilities GC cells. Moreover, closely associated with resistance chemotherapeutic agents Notably, this also discusses phenomenon crosstalk, highlighting interactions among their roles regulating pathways protein functions. Therefore, in-depth investigation into mechanisms targeted therapeutic strategies hold promise for advancing early diagnosis, treatment, prognostic evaluation GC, offering novel insights future directions.

Language: Английский

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Role of SIRT7 in Prostate Cancer Progression: New Insight Into Potential Therapeutic Target

Cancer Medicine, Journal Year: 2025, Volume and Issue: 14(7)

Published: April 1, 2025

ABSTRACT Prostate cancer (PCa) is the second most common in men worldwide, and understanding its molecular mechanisms crucial for developing effective treatment strategies. SIRT7, a NAD+‐dependent histone deacetylase, has emerged as key regulator PCa progression due to roles chromatin remodeling, DNA repair, transcriptional regulation. Analysis of 492 samples from The Cancer Genome Atlas (TCGA) via cBioPortal revealed that high SIRT7 expression associated with poor prognosis patients. Mechanistically, deacetylates H3 at lysine 18 (H3K18Ac), marker aggressive tumors, suppressing tumor suppressor genes promoting cell proliferation survival. Epithelial‐mesenchymal transition (EMT) cellular biological process which epithelial cells undergo specific morphological changes transform into characteristics mesenchymal cells. also regulates EMT, inhibiting lines reduces migration invasion, highlighting potential therapeutic target. In summary, clinical significance requires further research elucidate mechanisms. Developing inhibitors targeting SIRT7's deacetylase activity promising strategy. plays role regulating processes such proliferation, cycle, apoptosis through epigenetic control gene maintenance genomic stability. Therefore, may be target PCa, could have prognostic value patients, providing important guidance monitoring diagnosis by physicians.

Language: Английский

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Multi-omics identify ribosome related causal genes methylation, splicing, and expression in prostate cancer

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: May 12, 2025

Understanding the molecular underpinnings of prostate cancer remains a critical challenge in oncology. Ribosomes, essential cellular organelles responsible for protein synthesis, have emerged as potential regulators development. Previous studies suggest that dysfunction ribosomal processes may contribute significantly to progression. We used summary-data-based Mendelian randomization (SMR) and colocalization analysis, well single-cell investigate association between ribosome-related genes by integrating multi-omics. In this study, we employed multi-omics approach genomics transcriptomics data role cancer. Summary-level were obtained from The Prostate Cancer Association Group Investigate Associated Alterations Genome FinnGen studies. SMR analyses performed assess relevance gene-related signatures further analysis whether identified signal pairs shared causal genetic variants. Genes then validated with sequencing analysis. significant effects ribosome gene methylation on After mQTL, sQTL eQTL, two genes, NSUN4 MPHOSPH6. Methylation splicing at different sites showed increased decreased risks cancer, indicating complex regulation mechanisms. For instance, site cg10215817 was genetically associated risk (OR 1.20, 95% CI 1.10,1.30), while cg00937489 0.84, 0.74,0.94); chr1:46341497:46344801 1.11, 1.05-1.17) positively risk, chr1:46340919:46344801 0.95, 0.92-0.97) negatively risk. Expression indicated associations expression levels 1.06, 1.03-1.09; PPH4 = 0.79) MPHOSPH6 1.07, 1.04-1.10; 0.70). In-depth highly expresses epithelial cells, myeloid cells. study found This integrative underscores significance etiology. By elucidating mechanisms underlying dysfunction, our research identifies therapeutic targets mitigating disease These findings not only enhance understanding biology but also pave way personalized strategies targeting pathways improve clinical outcomes.

Language: Английский

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Structural Insights Into centSIRT6: Bioinformatic Analysis of N308K and A313S Substitution Effects

Bioinformatics and Biology Insights, Journal Year: 2025, Volume and Issue: 19

Published: May 1, 2025

Sirtuin 6 (SIRT6), a member of the class III histone deacetylase (HDAC) family, is crucial for maintenance general health and associated with increased life expectancy resistance to age-related diseases such as cancer metabolic disorders. A comparative analysis SIRT6 gene in Ashkenazi Jewish (AJ) centenarians noncentenarian controls found distinct allele, centSIRT6, enriched centenarian group. This allele features 2 linked substitutions, N308K A313S, exhibits enhanced functions, including more efficient suppression LINE1 retrotransposons, improved repair DNA double-strand breaks, efficiency cell killing. Notably, centSIRT6 shows lower activity but higher mono-adenosine diphosphate (ADP) ribosyl transferase compared wild-type enzyme. study used several bioinformatics tools explore structural changes caused by A313S substitutions elucidate how these alterations contribute enzymatic activities SIRT6. The results indicate that mutations reduce flexibility thus weakening its interactions acetyl-lysine strengthening ADP-ribose. research provides useful information future experimental studies further investigate molecular mechanisms centSIRT6.

Language: Английский

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Epigenetic Regulation of DNA Methylation and RNA Interference in Gastric Cancer: A 2024 Update

Biomedicines, Journal Year: 2024, Volume and Issue: 12(9), P. 2001 - 2001

Published: Sept. 3, 2024

Gastric cancer (GC) remains a significant public health concern because of its lethality, underscoring the need for deeper insights into molecular mechanisms. Recent studies have increasingly highlighted role epigenetic modifications as critical players in progression. Despite their importance, research specifically addressing factors GC is relatively scarce. This paper seeks to bridge that gap by examining recent literature elucidates landscape associated with GC. The investigation long noncoding RNAs (lncRNAs) has revealed substantial involvement gene dysregulation and alterations within tumors. Notably, lncRNAs such LINC00853 LINC01266 been identified contributors modulation expression. Furthermore, overexpression

Language: Английский

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Role of circular RNAs in DNA repair

RNA Biology, Journal Year: 2024, Volume and Issue: 21(1), P. 149 - 161

Published: Nov. 17, 2024

Circular RNAs (circRNAs) exhibit a wide range of activities that allow them to participate in numerous cellular processes and make relevant variety diseases. In this regard, key process which circRNAs are involved, is the focus article, DNA damage repair (DDR). This study aims illustrate how influence different pathways, with particular emphasis on underlying mechanisms. addition, potential medical applications knowledge discussed, particularly diagnosis, prognosis treatment sense, were found play crucial role by regulating expression activity proteins involved various pathways. They interacting their mRNAs, sponging miRNAs target these transcription factors bind promoters, modulating upstream signalling affecting mRNA translation. Furthermore, regulate directly them, sequestering specific compartments controlling activation or DDR signalling.

Language: Английский

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Dysregulation of protein succinylation and disease development

Frontiers in Molecular Biosciences, Journal Year: 2024, Volume and Issue: 11

Published: May 31, 2024

As a novel post-translational modification of proteins, succinylation is widely present in both prokaryotes and eukaryotes. By regulating protein translocation activity, particularly involved regulation gene expression, actively participates diverse biological processes such as cell proliferation, differentiation metabolism. Dysregulation closely related to many diseases. Consequently, it has increasingly attracted attention from basic clinical researchers. For thorough understanding dysregulation its implications for disease development, inflammation, tumors, cardiovascular neurological diseases, this paper provides comprehensive review the research progress on abnormal succinylation. This association with pathological will provide valuable directions prevention/treatment strategies well drug development.

Language: Английский

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