Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 180, P. 117477 - 117477
Published: Sept. 23, 2024
Language: Английский
Cancer Science, Journal Year: 2024, Volume and Issue: 115(4), P. 1209 - 1223
Published: Jan. 30, 2024
Abstract Abnormal activation of the oncogene YAP in Hippo pathway is a major feature liver cancer and inactivation MST1/2 has been shown to be responsible for overactivation that led tumorigenesis. However, mechanisms underlying dysregulation remain poorly understood. RNA‐seq analysis genome (KEGG) enrichment were used identify genes pathways regulated by SIRT7. qRT‐PCR, ChIP, luciferase assay investigate transcriptional regulation. Mass spectrometry, co‐immunoprecipitation immunoprecipitation exam protein–protein interaction post‐transcriptional modification. A xenograft mouse model was confirm effect SIRT7 inhibitors on hepatocellular carcinoma (HCC) proliferation vivo. We found suppresses MST1 both regulation modification, which turn promotes nuclear localization cancer. Mechanistically, we revealed transcription binding promoter inducing H3K18 deacetylation its region. In addition, directly binds deacetylates MST1, primes acetylation‐dependent ubiquitination protein degradation. clinical samples, confirmed negative correlation between levels, high expression correlated with elevated localization. specific inhibitor 2800Z sufficiently inhibited HCC growth disrupting SIRT7/MST1/YAP axis. Our data thus previously undescribed function regulating further proved targeting might provide novel therapeutic options treatment
Language: Английский
Citations
16
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
Citations
9
Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)
Published: Jan. 16, 2025
Sirtuin 7 (SIRT7), a member of the sirtuin family NAD+-dependent deacetylases, plays vital role in cancer, exhibiting context-dependent functions across various malignancies. Our study investigates SIRT7 depletion head and neck squamous cell carcinoma (HNSCC) progression. In vitro 3D organotypic models demonstrated that knock-out attenuates cancer viability, proliferation, motility as well induces downregulation migration- epithelial-mesenchymal transition (EMT)-related gene expression. Moreover, loss results slower organoid formation less invasive morphology, validated by vimentin downregulation. The potentiates S-phase arrest cycle progression after 5-FU treatment elevates ratio dead cells. Additionally, deletion reduces expression G1 phase-associated proteins, Cyclin D CDK4. Altogether, our highlights promising therapeutic target HNSCC, enhancing effectiveness modalities such combinational treatment.
Language: Английский
Citations
1
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
Citations
1
Cells, Journal Year: 2024, Volume and Issue: 13(12), P. 1054 - 1054
Published: June 18, 2024
Over the past decade, development of three-dimensional (3D) models has increased exponentially, facilitating unravelling fundamental and essential cellular mechanisms by which cells communicate with each other, assemble into tissues organs respond to biochemical biophysical stimuli under both physiological pathological conditions. This section presents a concise overview most recent updates on significant contribution different types 3D cell cultures including spheroids, organoids organ-on-chip bio-printed in advancing our understanding molecular mechanisms. The case studies presented include breast cancer (BC), endometriosis, liver microenvironment infections. In BC, establishment culture permitted visualization role cancer-associated fibroblasts delivery exosomes, as well significance physical properties extracellular matrix promoting proliferation invasion. approach also become valuable tool gaining insight general specific drug resistance. Given considerable heterogeneity offer more accurate representation vivo microenvironment, thereby identification translation novel targeted therapeutic strategies. advantages provided hepatic environment, conjunction high throughput characterizing various platforms, have enabled elucidation complex underlying threatening diseases. A limited number for gut skin infections been developed. However, profound comprehension spatial temporal interactions between microbes, host their environment may facilitate advancement vitro, ex disease models. Additionally, it pave way approaches diverse research fields. interested reader will find concluding remarks challenges prospects using discovering areas covered this review.
Language: Английский
Citations
7
Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16
Published: Jan. 29, 2025
Succinylation represents an emerging class of post-translational modifications (PTMs), characterized by the enzymatic or non-enzymatic transfer a negatively charged four-carbon succinyl group to ϵ-amino lysine residues, mediated succinyl-coenzyme A. Recent studies have highlighted involvement succinylation in various diseases, particularly cancer progression. Sirtuin 5 (SIRT5), member sirtuin family, has been extensively studied for its robust desuccinylase activity, alongside deacetylase function. To date, only limited number SIRT5 substrates identified. These mediate diverse physiological processes such as glucose oxidation, fatty acid ammonia detoxification, reactive oxygen species scavenging, anti-apoptosis, and inflammatory responses. The regulation these activities can occur through either same activity acting on different distinct targeting substrate. Aberrant expression closely linked tumorigenesis disease progression; however, role remains controversial. exhibits dual functionalities: it promote tumor proliferation, metastasis, drug resistance, metabolic reprogramming, thereby oncogene; conversely, also inhibit cell growth induce apoptosis, functioning suppressor gene. This review aims provide comprehensive overview current research status SIRT5. We discuss structural characteristics regulatory mechanisms, compare functions with other family members, elucidate mechanisms regulating activity. Specifically, we focus modification progression, highlighting how desuccinylation modulates development delineating underlying involved.
Language: Английский
Citations
0
Biochemical Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 116943 - 116943
Published: April 1, 2025
Language: Английский
Citations
0
International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 279, P. 135210 - 135210
Published: Aug. 30, 2024
Language: Английский
Citations
3
Trends in cancer, Journal Year: 2025, Volume and Issue: unknown
Published: March 1, 2025
Language: Английский
Citations
0
Cells, Journal Year: 2025, Volume and Issue: 14(6), P. 466 - 466
Published: March 20, 2025
Metabolic dysfunction leading to non-alcoholic fatty liver disease (NAFLD) exhibits distinct molecular and immune signatures that are influenced by factors like gut microbiota. The microbiome interacts with the via a bidirectional relationship gut–liver axis. Microbial metabolites, sirtuins, responses pivotal in different metabolic diseases. This extensive review explores complex multifaceted interrelationship between sirtuins microbiota, highlighting their importance health disease, particularly hepatocellular carcinoma (HCC). Sirtuins (SIRTs), classified as group of NAD+-dependent deacetylases, serve crucial modulators wide spectrum cellular functions, including pathways, inflammatory response, process senescence. Their subcellular localization diverse functions link them various conditions, NAFLD cancer. Concurrently, comprising microorganisms, significantly influences host metabolism responses. Recent findings indicate modulate microbiota composition function, while can affect sirtuin activity. is relevant disorders, where dysbiosis contributes progression. highlights recent on roles specific maintaining implications HCC development. Understanding these interactions offers potential therapeutic avenues for managing diseases linked dysregulation pathology.
Language: Английский
Citations
0