SIRT1 promotes glucolipid metabolic conversion to facilitate tumor development in colorectal carcinoma

Wei, Zhihao; Xia, Jianyu; Li, Jiatao; Cai, Jingshu; Shan, Juanjuan; Zhang, Chengcheng; Zhang, Lu; Wang, Ting; Qian, Cheng; Liu, Limei

doi:10.7150/ijbs.76704

Cited by 15 publications

(5 citation statements)

References 38 publications

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“…Sirt1 regulates a wide range of physiological and pathological processes through deacetylation. [51][52][53] Our findings corroborate that Sirt1 regulated necroptosis through modulation of deacetylation modifications by interaction with RIPK1, consistent with previous study. 54 Our findings corroborate that Sirt1 regulated necroptosis through modulation of deacetylation modifications by interaction with RIPK1, consistent with previous study.…”

Section: Discussionsupporting

confidence: 92%

Sirt1 Deficiency Promotes Age-Related AF Through Enhancing Atrial Necroptosis by Activation of RIPK1 Acetylation

Jin,

Zhang,

Zhou

et al. 2024

Circ: Arrhythmia and Electrophysiology

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BACKGROUND: Aging is one of the most potent risk determinants for the onset of atrial fibrillation (AF). Sirts (sirtuins) have been implicated in the pathogenesis of cardiovascular disease, and their expression declines with aging. However, whether Sirts involved in age-related AF and its underlying mechanisms remain unknown. The present study aims to explore the role of Sirts in age-related AF and delineate the underlying molecular mechanisms. METHODS: Sirt1 levels in the atria of both elderly individuals and aging rats were evaluated using quantitative real-time PCR and Western blot analysis. Mice were engineered to specifically knockout Sirt1 in the atria and right ventricle (Sirt1 mef2c/mef2c ). Various techniques, such as echocardiography, atrial electrophysiology, and protein acetylation modification omics were employed. Additionally, coimmunoprecipitation was utilized to substantiate the interaction between Sirt1 and RIPK1 (receptor-interacting protein kinase 1). RESULTS: We discerned that among the diverse subtypes of sirtuin proteins, only Sirt1 expression was significantly diminished in the atria of elderly people and aged rats. The Sirt1 mef2c/mef2c mice exhibited an enlarged atrial diameter and heightened vulnerability to AF. Acetylated proteomics and cell experiments identified that Sirt1 deficiency activated atrial necroptosis through increasing RIPK1 acetylation and subsequent pseudokinase MLKL (mixed lineage kinase domain-like protein) phosphorylation. Consistently, necroptotic inhibitor necrosulfonamide mitigated atrial necroptosis and diminished both the atrial diameter and AF susceptibility of Sirt1 mef2c/mef2c mice. Resveratrol prevented age-related AF in rats by activating atrial Sirt1 and inhibiting necroptosis. CONCLUSIONS: Our findings first demonstrated that Sirt1 exerts significant efficacy in countering age-related AF by impeding atrial necroptosis through regulation of RIPK1 acetylation, highlighting that the activation of Sirt1 or the inhibition of necroptosis could potentially serve as a therapeutic strategy for age-related AF.

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Section: Discussionsupporting

confidence: 92%

Sirt1 Deficiency Promotes Age-Related AF Through Enhancing Atrial Necroptosis by Activation of RIPK1 Acetylation

Jin,

Zhang,

Zhou

et al. 2024

Circ: Arrhythmia and Electrophysiology

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“…Interestingly, c-Myc, one of the Myc family, known as oncogenes [ 16 , 17 ], regulates glucose and glutamine metabolism in several cancers, including prostate cancer [ 18 , 19 ]. In addition, silent information regulator 1 (SIRT1) enhances tumorigenesis and metastasis via the deacetylation of tumor suppressors [ 20 ] and also increases glucolipid metabolic conversion to facilitate cancer progression [ 21 ]. Likewise, WNT/β-catenin signaling promotes self-renewal or expansion in prostate cancer stem cells [ 22 ] and modulates aerobic glycolysis [ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

The Apoptotic and Anti-Warburg Effects of Brassinin in PC-3 Cells via Reactive Oxygen Species Production and the Inhibition of the c-Myc, SIRT1, and β-Catenin Signaling Axis

Kwon,

Ahn,

Lee

et al. 2023

IJMS

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Though Brassinin is known to have antiangiogenic, anti-inflammatory, and antitumor effects in colon, prostate, breast, lung, and liver cancers, the underlying antitumor mechanism of Brassinin is not fully understood so far. Hence, in the current study, the apoptotic mechanism of Brassinin was explored in prostate cancer. Herein, Brassinin significantly increased the cytotoxicity and reduced the expressions of pro-Poly ADP-ribose polymerase (PARP), pro-caspase 3, and B-cell lymphoma 2 (Bcl-2) in PC-3 cells compared to DU145 and LNCaP cells. Consistently, Brassinin reduced the number of colonies and increased the sub-G1 population and terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL)-positive cells in the PC-3 cells. Of note, Brassinin suppressed the expressions of pyruvate kinase-M2 (PKM2), glucose transporter 1 (GLUT1), hexokinase 2 (HK2), and lactate dehydrogenase (LDH) as glycolytic proteins in the PC-3 cells. Furthermore, Brassinin significantly reduced the expressions of SIRT1, c-Myc, and β-catenin in the PC-3 cells and also disrupted the binding of SIRT1 with β-catenin, along with a protein–protein interaction (PPI) score of 0.879 and spearman’s correlation coefficient of 0.47 being observed between SIRT1 and β-catenin. Of note, Brassinin significantly increased the reactive oxygen species (ROS) generation in the PC-3 cells. Conversely, ROS scavenger NAC reversed the ability of Brassinin to attenuate pro-PARP, pro-Caspase3, SIRT1, and β-catenin in the PC-3 cells. Taken together, these findings support evidence that Brassinin induces apoptosis via the ROS-mediated inhibition of SIRT1, c-Myc, β-catenin, and glycolysis proteins as a potent anticancer candidate.

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“…[125] In OSF-derived OSCC, our observations indicate a preference for tumor cells to derive energy through the fatty acid 𝛽-oxidation pathway, aligning with findings reported in other tumors. [126,127] Amino acid metabolism is an important nitrogen metabolic pathway in the tumor microenvironment, and tumors often undergo amino acid metabolic reprogramming to meet the increased nitrogen metabolic demands. [128] Since Leeuwenhoek [129] first discovered spermine in 1678, polyamine metabolism has been recognized as a crucial part of intracellular nitrogen metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…[ 125 ] In OSF‐derived OSCC, our observations indicate a preference for tumor cells to derive energy through the fatty acid β ‐oxidation pathway, aligning with findings reported in other tumors. [ 126 , 127 ]…”

Section: Discussionmentioning

confidence: 99%

Spatial Transcriptomic and Metabolomic Landscapes of Oral Submucous Fibrosis‐Derived Oral Squamous Cell Carcinoma and its Tumor Microenvironment

Zhi,

Wang,

et al. 2024

Advanced Science

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In South and Southeast Asia, the habit of chewing betel nuts is prevalent, which leads to oral submucous fibrosis (OSF). OSF is a well‐established precancerous lesion, and a portion of OSF cases eventually progress to oral squamous cell carcinoma (OSCC). However, the specific molecular mechanisms underlying the malignant transformation of OSCC from OSF are poorly understood. In this study, the leading‐edge techniques of Spatial Transcriptomics (ST) and Spatial Metabolomics (SM) are integrated to obtain spatial location information of cancer cells, fibroblasts, and immune cells, as well as the transcriptomic and metabolomic landscapes in OSF‐derived OSCC tissues. This work reveals for the first time that some OSF‐derived OSCC cells undergo partial epithelial–mesenchymal transition (pEMT) within the in situ carcinoma (ISC) region, eventually acquiring fibroblast‐like phenotypes and participating in collagen deposition. Complex interactions among epithelial cells, fibroblasts, and immune cells in the tumor microenvironment are demonstrated. Most importantly, significant metabolic reprogramming in OSF‐derived OSCC, including abnormal polyamine metabolism, potentially playing a pivotal role in promoting tumorigenesis and immune evasion is discovered. The ST and SM data in this study shed new light on deciphering the mechanisms of OSF‐derived OSCC. The work also offers invaluable clues for the prevention and treatment of OSCC.

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SIRT1 promotes glucolipid metabolic conversion to facilitate tumor development in colorectal carcinoma

Cited by 15 publications

References 38 publications

Sirt1 Deficiency Promotes Age-Related AF Through Enhancing Atrial Necroptosis by Activation of RIPK1 Acetylation

Sirt1 Deficiency Promotes Age-Related AF Through Enhancing Atrial Necroptosis by Activation of RIPK1 Acetylation

The Apoptotic and Anti-Warburg Effects of Brassinin in PC-3 Cells via Reactive Oxygen Species Production and the Inhibition of the c-Myc, SIRT1, and β-Catenin Signaling Axis

Spatial Transcriptomic and Metabolomic Landscapes of Oral Submucous Fibrosis‐Derived Oral Squamous Cell Carcinoma and its Tumor Microenvironment

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