Mitochondrial sirtuins in stem cells and cancer

Jaiswal, Amit; Zhu, Xudong; Ju, Zhenyu; Saretzki, Gabriele

doi:10.1111/febs.15879

Cited by 23 publications

(18 citation statements)

References 185 publications

(380 reference statements)

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“…ZEB1 is the key transcription factor of EMT, and it drives non-CSC to CSCs. Histone acetylation of the ZEB1 poises its chromatin and promotes EMT’s acquisition of CSC features in breast cancer [ 400 , 401 , 402 , 403 ]. Hypoxia inhibits the oxygen-dependent H3K27me3 demethylases and increases ZEB1 expression and prompts EMT’s acquisition of a CSCs phenotype [ 403 ].…”

Section: Epigenetics In Normal Development and Tumorigenesismentioning

confidence: 99%

An Epigenetic Role of Mitochondria in Cancer

Liu

Chen

Wang

et al. 2022

Cells

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Mitochondria are not only the main energy supplier but are also the cell metabolic center regulating multiple key metaborates that play pivotal roles in epigenetics regulation. These metabolites include acetyl-CoA, α-ketoglutarate (α-KG), S-adenosyl methionine (SAM), NAD+, and O-linked beta-N-acetylglucosamine (O-GlcNAc), which are the main substrates for DNA methylation and histone post-translation modifications, essential for gene transcriptional regulation and cell fate determination. Tumorigenesis is attributed to many factors, including gene mutations and tumor microenvironment. Mitochondria and epigenetics play essential roles in tumor initiation, evolution, metastasis, and recurrence. Targeting mitochondrial metabolism and epigenetics are promising therapeutic strategies for tumor treatment. In this review, we summarize the roles of mitochondria in key metabolites required for epigenetics modification and in cell fate regulation and discuss the current strategy in cancer therapies via targeting epigenetic modifiers and related enzymes in metabolic regulation. This review is an important contribution to the understanding of the current metabolic-epigenetic-tumorigenesis concept.

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Section: Epigenetics In Normal Development and Tumorigenesismentioning

confidence: 99%

An Epigenetic Role of Mitochondria in Cancer

Liu

Chen

Wang

et al. 2022

Cells

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“…The sirtuin family is highly related with important metabolic regulatory pathways in prokaryotes and eukaryotes, and is involved in regulating various biological functions such as apoptosis, metabolism, stress responses, aging, differentiation and cell cycle progression (35). Sirt3, one of seven members of the sirtuin family, is involved in the pathology of neurological diseases by regulating gene expression and enzyme activity related to oxidative metabolism and stress response (36).…”

Section: Discussionmentioning

confidence: 99%

Gastrodin exerts protective effects in reactive TNC1 astrocytes via regulation of the Notch signaling pathway

Zhang¹,

Yang²,

Wu³

et al. 2021

Ann Transl Med

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Background: Gastrodin (GAS) has been proven to play a therapeutic role in a variety of neurological diseases by affecting activated astrocytes, however, the underlying mechanisms have not been fully illustrated.This study aimed to investigate if GAS exerts the neuroprotective effect through regulating the Notch signaling pathway involved in reactive astrocytes.Methods: Astrocyte cell lines (TNC1 cells) were cultured in vitro. The hypoxic-ischemic cell model was prepared using the oxygen-glucose deprivation (OGD) method, GAS's pretreatment concentration was 0.34 mM, intervention for 1 hour. Cell counting kit-8 (CCK-8) assay, Transwell migration assay, immunofluorescent staining (double staining), and Western blotting were used to observe the effects of OGD or GAS interference on the function of astrocytes, and the changes of key protein expressions in the Notch signaling pathway were analyzed.Results: GAS had no obvious toxic effect on TNC1 astrocytes under physiological conditions. Following OGD, GAS can not only improve cell viability and migration, but also regulate the production of inflammatory mediators. We also found that OGD significantly increased the expression of key proteins related to the Notch signaling pathway, Notch-1, intracellular Notch receptor domain (NICD), recombining binding protein suppressor of hairless (RBP-JK), transcription factor hairy and enhancer of split-1 (Hes-1) in TNC1 astrocytes, which was significantly inhibited by GAS. In addition, GAS inhibited the OGD-induced expression of TNC1 astrocyte tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β), and enhanced the expression of nutrient factors, including brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1). The Notch signaling pathway specific inhibitor, N-[N-(3,5-Difluorophenacetyl)-1-alany1]-S-phenyglycine t-butylester (DAPT), could significantly enhance the effect of GAS on TNC1 astrocytes after OGD, such as the inhibition of inflammatory factors and the up-regulation of neurotrophic factors.Conclusions: GAS exerts dual effects on astrocytes via regulation of the Notch signaling pathway. We found that it could inhibit the pro-inflammatory factors mediated by astrocytes, and also promote the secretion of neurotrophic factors by astrocytes. These results provide a new biological mechanism for the treatment of neuroinflammatory diseases by GAS.

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“…Furthermore, the SIRT family proteins have conserved domains in their core catalytic activities, with SIRT1, SIRT2 and SIRT3 designated as class I; SIRT4 designated as class II; SIRT5 designated as class III; and SIRT6 and SIRT7 designated as class IV (Figure 1 )[ 4 ]. Sirtuins are involved in the regulation of various biological functions, such as apoptosis, metabolism, stress response, aging, differentiation and cell cycle progression[ 5 ]. However, while the role of sirtuins in cancer progression has been investigated over the past few years, their precise role remains difficult to characterize, as they have both cancer-promoting and cancer-suppressing properties, depending on the type of cancer[ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Role of sirtuins in esophageal cancer: Current status and future prospects

Otsuka¹,

Hayano²,

Matsubara³

2022

WJGO

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Esophageal cancer (EC) is a malignant cancer that still has a poor prognosis, although its prognosis has been improving with the development of multidisciplinary treatment modalities such as surgery, chemotherapy and radiotherapy. Therefore, identifying specific molecular markers that can be served as biomarkers for the prognosis and treatment response of EC is highly desirable to aid in the personalization and improvement of the precision of medical treatment. Sirtuins are a family of nicotinamide adenine dinucleotide (NAD+)-dependent proteins consisting of seven members (SIRT1-7). These proteins have been reported to be involved in the regulation of a variety of biological functions including apoptosis, metabolism, stress response, senescence, differentiation and cell cycle progression. Given the variety of functions of sirtuins, they are speculated to be associated in some manner with cancer progression. However, while the role of sirtuins in cancer progression has been investigated over the past few years, their precise role remains difficult to characterize, as they have both cancer-promoting and cancer-suppressing properties, depending on the type of cancer. These conflicting characteristics make research into the nature of sirtuins all the more fascinating. However, the role of sirtuins in EC remains unclear due to the limited number of reports concerning sirtuins in EC. We herein review the current findings and future prospects of sirtuins in EC.

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Mitochondrial sirtuins in stem cells and cancer

Cited by 23 publications

References 185 publications

An Epigenetic Role of Mitochondria in Cancer

An Epigenetic Role of Mitochondria in Cancer

Gastrodin exerts protective effects in reactive TNC1 astrocytes via regulation of the Notch signaling pathway

Role of sirtuins in esophageal cancer: Current status and future prospects

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