Research Progress of Sirtuin4 in Cancer

Bai, Yalai; Yang, Jiani; Cui, Ying; Yao, Yuanfei; Wu, Feng; Liu, Caiqi; Fan, Xuetong; Zhang, Yanqiao

doi:10.3389/fonc.2020.562950

Cited by 11 publications

(18 citation statements)

References 109 publications

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“…The prediction by the JASPAR database suggested that FOXQ1 might regulate the transcription of the Sirt4 gene. Sirt4 is considered as a sensor of mitochondrial metabolism, which has a variety of catalytic activities and is involved in cellular metabolism, oxidative stress, and mitochondrial energy metabolism, and has an important role in many metabolic processes 21,29 . Among the seven mammalian sirtuins, only Sirt1‐3 were initially found to possess robust deacetylase activity.…”

Section: Discussionmentioning

confidence: 99%

“…The JASPAR database (https://jaspar.genereg.net/) predicted the presence of multiple binding sites for FOXQ1 in the promoter region of the Sirt4 gene. Sirt4 is a member of the highly conserved sirtuins protein family that regulates energy metabolism in the mitochondria 21 . Anand et al demonstrated that Sirt4 up‐regulation affected mitochondrial fusion and/or fission and accelerated the clearance of dysfunctional mitochondria, thereby regulating mitochondrial function 22 .…”

Section: Introductionmentioning

confidence: 99%

“…Sirt4 is a member of the highly conserved sirtuins protein family that regulates energy metabolism in the mitochondria. 21 Anand et al demonstrated that Sirt4 up-regulation affected mitochondrial fusion and/or fission and accelerated the clearance of dysfunctional mitochondria, thereby regulating mitochondrial function. 22 Furthermore, Zhang et al found that the up-regulation of Sirt4 inhibited pyroptosis of podocytes mediated by inflammasome activation, which reduced kidney injury in DKD, suggesting that reduced Sirt4 expression induced the occurrence and development of DKD.…”

Section: Introductionmentioning

confidence: 99%

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miR‐124‐3p improves mitochondrial function of renal tubular epithelial cells in db/db mice

Liang

Yuan

et al. 2023

The FASEB Journal

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Diabetic kidney disease (DKD) is one of the most serious complications of diabetes mellitus (DM) and the main cause of end‐stage renal failure. However, the pathogenesis of DKD is complicated. In this study, we found that miR‐124‐3p plays a key role in regulating renal mitochondrial function and explored its possible mechanism in DKD progression by performing a series of in vitro and in vivo experiments. Decreased expression of miR‐124‐3p was found in db/db mice compared to db/m mice. Moreover, miR‐124‐3p down‐regulated FOXQ1 by targeting FOXQ1 mRNA 3′‐UTR in NRK‐52E cells. Also, an increase in FOXQ1 and down‐regulation of Sirt4 were found in db/db mouse kidney and renal tubular epithelial cells cultured with high glucose and high lipid. Overexpression of FOXQ1 could further down‐regulate the expression of Sirt4 and aggravate the damage of mitochondria. Conversely, the knockdown of the FOXQ1 gene induced Sirt4 expression and partially restored mitochondrial function. To verify the effects of miR‐124‐3p on Sirt4 and mitochondria, we found that miR‐124‐3p mimics could up‐regulate Sirt4 and inhibit ROS production and MitoSOX, thus restoring the number and morphology of mitochondria. These results showed that under high‐glucose and high‐lipid conditions, the down‐regulation of miR‐124‐3p induces FOXQ1 in renal tubular epithelial cells, which in turn suppresses Sirt4 and leads to mitochondrial dysfunction, promoting the development of DKD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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miR‐124‐3p improves mitochondrial function of renal tubular epithelial cells in db/db mice

Liang

Yuan

et al. 2023

The FASEB Journal

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“…The activity of SIRT4 in CRC is still relatively unknown. However, many findings point out the tumor suppressor role of this mitochondrial SIRT able to counter the gaining of malignant properties from cancerous cells, underlining that SIRT4 expression is lower in CRC compared to normal tissue [ 121 ]. SIRT4 activity affects glutamine metabolism repressing the activity of glutamate dehydrogenase (GDH) and abrogating alpha-ketoglutarate (αKG) formation ( Figure 3 ) [ 122 ].…”

Section: Mitochondrial Sirtuins and Crcmentioning

confidence: 99%

Mitochondrial Sirtuins in Chronic Degenerative Diseases: New Metabolic Targets in Colorectal Cancer

Colloca¹,

Balestrieri²,

Anastasio³

et al. 2022

IJMS

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Sirtuins (SIRTs) are a family of class III histone deacetylases (HDACs) consisting of seven members, widely expressed in mammals. SIRTs mainly participate in metabolic homeostasis, DNA damage repair, cell survival, and differentiation, as well as other cancer-related biological processes. Growing evidence shows that SIRTs have pivotal roles in chronic degenerative diseases, including colorectal cancer (CRC), the third most frequent malignant disease worldwide. Metabolic alterations are gaining attention in the context of CRC development and progression, with mitochondrion representing a crucial point of complex and intricate molecular mechanisms. Mitochondrial SIRTs, SIRT2, SIRT3, SIRT4 and SIRT5, control mitochondrial homeostasis and dynamics. Here, we provide a comprehensive review on the latest advances on the role of mitochondrial SIRTs in the initiation, promotion and progression of CRC. A deeper understanding of the pathways by which mitochondrial SIRTs control CRC metabolism may provide new molecular targets for future innovative strategies for CRC prevention and therapy.

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“…Sirtuin 4 is one of highly conserved NAD + -dependent protein deacylases that regulate post-translational modifications of various proteins [16,17]. SIRT4 possesses deactylation, lipoamidase and adenosine diphosphate (ADP)/ribosyltransferase activity to regulate catabolism of multiple nutrients, including fatty oxidation, lipid and amino acids [18][19][20][21][22][23][24][25]. SIRT4 has been shown to act as an ADP-ribosyltrasferase to ADP-ribosylate glutamate dehydrogenase, which promotes the metabolism of glutamate and glutamine [18,24].…”

Section: Introductionmentioning

confidence: 99%

mTORC1-c-Myc pathway rewires methionine metabolism for HCC progression through suppressing SIRT4 mediated ADP ribosylation of MAT2A

Zhao

Liu

et al. 2022

Cell Biosci

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Background Exploiting cancer metabolism during nutrient availability holds immense potential for the clinical and therapeutic benefits of hepatocellular carcinoma (HCC) patients. Dietary methionine is a metabolic dependence of cancer development, but how the signal transduction integrates methionine status to achieve the physiological demand of cancer cells remains unknown. Methods Low or high levels of dietary methionine was fed to mouse models with patient-derived xenograft or diethyl-nitrosamine induced liver cancer. RNA sequence and metabolomics were performed to reveal the profound effect of methionine restriction on gene expression and metabolite changes. Immunostaining, sphere formation assays, in vivo tumourigenicity, migration and self-renewal ability were conducted to demonstrate the efficacy of methionine restriction and sorafenib. Results We discovered that mTORC1-c-Myc-SIRT4 axis was abnormally regulated in a methionine-dependent manner and affected the HCC progression. c-Myc rewires methionine metabolism through TRIM32 mediated degradation of SIRT4, which regulates MAT2A activity by ADP-ribosylation on amino acid residue glutamic acid 111. MAT2A is a key enzyme to generate S-adenosylmethionine (SAM). Loss of SIRT4 activates MAT2A, thereby increasing SAM level and dynamically regulating gene expression, which triggers the high proliferation rate of tumour cells. SIRT4 exerts its tumour suppressive function with targeted therapy (sorafenib) by affecting methionine, redox and nucleotide metabolism. Conclusions These findings establish a novel characterization of the signaling transduction and the metabolic consequences of dietary methionine restriction in malignant liver tissue of mice. mTORC1, c-Myc, SIRT4 and ADP ribosylation site of MAT2A are promising clinical and therapeutic targets for the HCC treatment.

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Research Progress of Sirtuin4 in Cancer

Cited by 11 publications

References 109 publications

miR‐124‐3p improves mitochondrial function of renal tubular epithelial cells in db/db mice

miR‐124‐3p improves mitochondrial function of renal tubular epithelial cells in db/db mice

Mitochondrial Sirtuins in Chronic Degenerative Diseases: New Metabolic Targets in Colorectal Cancer

mTORC1-c-Myc pathway rewires methionine metabolism for HCC progression through suppressing SIRT4 mediated ADP ribosylation of MAT2A

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