Deacetylation of Transcription Factors in Carcinogenesis

Hałasa, Marta; Adamczuk, Kamila; Adamczuk, Grzegorz; Afshan, Syeda; Stepulak, Andrzej; Cybulski, Marek; Wawruszak, Anna

doi:10.3390/ijms222111810

Cited by 8 publications

(9 citation statements)

References 117 publications

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“…Chromatin alteration by histone modification has epigenetic effects on various cellular processes such as DNA recombination, cell cycle progression, DNA repair, and apoptosis ( Chrun et al ., 2017 ). Histone deacetylases (HDACs) are known for their ability to remove acetyl groups at lysine residues in histone proteins, but recent several studies have demonstrated that they deacetylate both histones and non-histone proteins ( Mariadason, 2008 ; Ocker, 2010 ; Halasa et al ., 2021 ). The class III HDAC member sirtuin (SIRT), is a highly conserved group of seven proteins in humans.…”

Section: Introductionmentioning

confidence: 99%

MHY2251, a New SIRT1 Inhibitor, Induces Apoptosis via JNK/p53 Pathway in HCT116 Human Colorectal Cancer Cells

Kang

Kwon

Jang

et al. 2022

Biomol Ther (Seoul)

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Despite the recent advances in diagnostic and surgical techniques, colorectal cancer (CRC) remains the third most frequently diagnosed cancer and second most common cause of cancer-related mortality worldwide (Li, 2018). CRC is mainly treated by surgical removal, radiotherapy, chemotherapy, or a combination of surgery and chemotherapy (Yang et al., 2017). Despite various treatment strategies, many patients with CRC continue to experience relapse-hence, improved chemotherapeutic agents that can effectively induce apoptosis in CRC cells are urgently needed.Apoptosis involves two types of signaling pathways. The extrinsic pathway is initiated by the binding of specific receptors on the cell surface, called death receptors, with an extracellular ligand. This involves the binding of Fas receptors, known as differentiation clusters, to Fas ligands, and tumor necrosis factor (TNF) receptors to TNF (Ashkenazi, 2008;Fulda, 2015). These binding events induce the activation of caspase 8 in the intracellular domain of the receptor (O'Brien and Kirby, 2008;Wong, 2011). Activated caspase 8 can affect mitochondria or further activate caspase 3 (Ashkenazi, 2008). The intrinsic pathway is initiated by the loss of mitochondrial membrane potential, resulting in the release of internalized cytochrome c into the cytoplasm (Saelens et al., 2004). The released cytochrome c activates caspase 3 by forming a complex called the apoptosome with apoptosis protease activator 1 and caspase 9 (Elmore, 2007). A family of proteins called B-cell lymphoma

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Section: Introductionmentioning

confidence: 99%

MHY2251, a New SIRT1 Inhibitor, Induces Apoptosis via JNK/p53 Pathway in HCT116 Human Colorectal Cancer Cells

Kang

Kwon

Jang

et al. 2022

Biomol Ther (Seoul)

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“…Acetylation and deacetylation of lysine residues are reversibly regulated by acetyltransferase and deacetylase, which are implicated in tumour progression and metastasis. 48 To further unearth the enzymes related to the regulation of ACLY acetylation level, acetyltransferase (PCAF) and deacetylase (HDAC1 and SIRT2) were selected for further study, we found that ACLY had significant interaction with PCAF and SIRT2 in ESCC cells, but not HDAC1. However, because SIRT2 was significantly enriched in the protein complex, we used SIRT2 as Co-IP antibody for reverse verification by immunoprecipitation.…”

Section: Discussionmentioning

confidence: 99%

SIRT2‐mediated deacetylation of ACLY promotes the progression of oesophageal squamous cell carcinoma

Zhang,

Xu,

et al. 2024

J Cellular Molecular Medi

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ATP citrate lyase (ACLY), as a key enzyme in lipid metabolism, plays an important role in energy metabolism and lipid biosynthesis of a variety of tumours. Many studies have shown that ACLY is highly expressed in various tumours, and its pharmacological or gene inhibition significantly inhibits tumour growth and progression. However, the roles of ACLY in oesophageal squamous cell carcinoma (ESCC) remain unclear. Here, our data showed that ACLY inhibitor significantly attenuated cell proliferation, migration, invasion and lipid synthesis in different ESCC cell lines, whereas the proliferation, migration, invasion and lipid synthesis of ESCC cells were enhanced after ACLY overexpression. Furthermore, ACLY inhibitor dramatically suppressed tumour growth and lipid metabolism in ESCC cells xenografted tumour model, whereas ACLY overexpression displayed the opposite effect. Mechanistically, ACLY protein harboured acetylated modification and interacted with SIRT2 protein in ESCC cells. The SIRT2 inhibitor AGK2 significantly increased the acetylation level of ACLY protein and inhibited the proliferation and migration of ESCC cells, while overexpression of ACLY partially reversed the inhibitory effect of AGK2 on ESCC cells. Overall, these results suggest that targeting the SIRT2/ACLY signalling axis may be a potential therapeutic strategy for ESCC patients.

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“…Histone acetylation and deacetylation are among the most common post-translational modifications. HDACs maintain a dynamic balance between acetylation and deacetylation ( 20 ), thereby regulating cell proliferation, apoptosis, metastasis, and cell cycle progression and affecting histone properties and their biological functions ( 21 , 22 ). Previous studies have demonstrated that HDAC5 is differentially expressed in tumor tissues.…”

Section: Discussionmentioning

confidence: 99%

High HDAC5 expression correlates with a poor prognosis and the tumor immune microenvironment in gastric cancer

Li¹,

Hu²,

Yu³

et al. 2022

Ann Transl Med

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Background: Gastric cancer (GC) is one of the most common malignant tumors worldwide and has a poor prognosis. Previous studies have confirmed differential histone deacetylase 5 (HDAC5) expression in various common tumors. HDAC5 is also associated with prognosis and plays a role in cancer cell proliferation, invasion, and metastasis, as well as the tumor immune microenvironment (TIME). However, HDAC5 in GC is not well understood. The aims of study were to investigate the HDAC5 expression correlates with prognosis and the TIME in GC.Methods: A total of 355 tumor tissues and 300 matched paracancerous tissues were collected from GC patients who underwent radical surgery. The correlation between clinicopathological characteristics, immune-related factors and HDAC5 expression were analyzed. Univariate and multivariate Cox regression analyses were used to confirm the independent factors affecting the prognosis of GC. Survival curves were plotted using the Kaplan-Meier method. Furthermore, the stomach adenocarcinoma (STAD) dataset was downloaded from The Cancer Genome Atlas (TCGA). The expression levels of HDAC5 were defined as high or low using the gene set variance analysis (GSVA) package. Identification of differential immune infiltrating cells was performed by single sample gene set enrichment analysis (ssGSEA). Results:The positive expression rate of HDAC5 was higher in tumor tissues than in paracancerous tissues (38.87% vs. 14.67%, P<0.001). Univariate and multivariate Cox analyses showed that HDAC5 was an independent factor affecting the prognosis of GC. The HDAC5 expression levels were correlated with age (P=0.046), smoking history (P=0.001), Lauren type (P=0.042), and pM stage (P=0.012). Furthermore, these levels were correlated with CD3 + T cells (P<0.001), CD4 + T cells (P<0.001), CD8 + T cells (P<0.001) and PD-L1 (P=0.001). Further analysis of patients in TCGA cohort confirmed the association between HDAC5 and activated CD4 T cells, activated CD8 T cells, and other immune infiltrating cells.Conclusions: HDAC5 is highly expressed in tumor tissues and is an independent factor affecting the prognosis of GC. Additionally, HDAC5 can regulate the TIME of GC and is a potential target for immunotherapy.

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Deacetylation of Transcription Factors in Carcinogenesis

Cited by 8 publications

References 117 publications

MHY2251, a New SIRT1 Inhibitor, Induces Apoptosis via JNK/p53 Pathway in HCT116 Human Colorectal Cancer Cells

MHY2251, a New SIRT1 Inhibitor, Induces Apoptosis via JNK/p53 Pathway in HCT116 Human Colorectal Cancer Cells

SIRT2‐mediated deacetylation of ACLY promotes the progression of oesophageal squamous cell carcinoma

High HDAC5 expression correlates with a poor prognosis and the tumor immune microenvironment in gastric cancer

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