Further Characterization of HDAC and SIRT Gene Expression Patterns in Pancreatic Cancer and Their Relation to Disease Outcome

Ouaïssi, Mehdi; Silvy, Françoise; Loncle, Céline; Silva, Diva Ferraz da; Abreu, Carla M.; Martínez, Emmanuelle; Berthezene, P.; Cadra, Sophie; Treut, Yves Patrice Le; Hardwigsen, Jean; Sastre, Bernard; Sielezneff, I.; Benkoël, L; Delgrande, Jean; Ouaissi, Ali; Iovanna, Juan; Lagadic‐Gossmann, Dominique; Mas, Eric

doi:10.1371/journal.pone.0108520

Cited by 34 publications

(26 citation statements)

References 32 publications

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“…We also show the clinical characteristics of all 6 patients in Table 1. It has been reported that invasiveness, inflammation and other disease outcomes are related to HDAC levels and activity 39, 64-66. Invasiveness is one of the vital characteristics of osteosarcoma and it was reported to be related to matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9)67, 68.…”

Section: Discussionmentioning

confidence: 99%

Histone Deacetylase Inhibitor Trichostatin a Promotes the Apoptosis of Osteosarcoma Cells through p53 Signaling Pathway Activation

Deng¹,

Liu²,

Jin³

et al. 2016

Int. J. Biol. Sci.

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Purpose: The purpose of this study was to investigate the profile of histone deacetylase (HDAC) activity and expression in osteosarcoma cells and tissues from osteosarcoma patients and to examine the mechanism by which a histone deacetylase (HDAC) inhibitor, Trichostatin A (TSA), promotes the apoptosis of osteosarcoma cells.Methods: HDAC activity and histone acetyltransferase (HAT) activity were determined in nuclear extracts of MG63 cells, hFOB 1.19 cells and tissues from 6 patients with primary osteosarcoma. The protein expression of Class I HDACs (1, 2, 3 and 8) and the activation of the p53 signaling pathway were examined by Western blot. Cell growth and apoptosis were determined by 3-(4, 5-dimethyl-2-thiazolyl)-2H-tetrazolium bromide (MTT) assay and flow cytometry, respectively.Results: Nuclear HDAC activity and class I HDAC expression were significantly higher in MG63 cells than in hFOB 1.19 cells, and a similar trend was observed in the human osteosarcoma tissues compared with the paired adjacent non-cancerous tissues. TSA significantly inhibited the growth of MG63 cells and promoted apoptosis in a dose-dependent manner through p53 signaling pathway activation.Conclusion: Class I HDACs play a central role in the pathogenesis of osteosarcoma, and HDAC inhibitors may thus have promise as new therapeutic agents against osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

Histone Deacetylase Inhibitor Trichostatin a Promotes the Apoptosis of Osteosarcoma Cells through p53 Signaling Pathway Activation

Deng¹,

Liu²,

Jin³

et al. 2016

Int. J. Biol. Sci.

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“…However, differentiating the exact role of HDAC in acinar proliferation during pancreatitis is precluded by the interference of the inflammatory reaction, thus we cannot exclude the possibility that MS-275 directly inhibits, to some extent, cell cycle progression in acinar cells. Increased HDAC activity is found in human pancreatic cancer cells (McCleary-Wheeler et al, 2013;Ouaissi et al, 2014), and it is essential for cell proliferation, NF-κB activation and EMT transition (Lehmann et al, 2009;Aghdassi et al, 2012). However, since the role of HDAC in pancreatic cancer cells cannot be directly translated to non-transformed acinar cells, additional non-tumour-based experimental models are required to address the role of HDAC in acinar cell proliferation.…”

Section: Ms-275 and Acinar Cell Proliferationmentioning

confidence: 99%

Class I histone deacetylase inhibition improves pancreatitis outcome by limiting leukocyte recruitment and acinar‐to‐ductal metaplasia

Bombardo

Saponara

Malagola

et al. 2017

British J Pharmacology

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BACKGROUND AND PURPOSEPancreatitis is a common inflammation of the pancreas with rising incidence in many countries. Despite improvements in diagnostic techniques, the disease is associated with high risk of severe morbidity and mortality and there is an urgent need for new therapeutic interventions. In this study, we evaluated whether histone deacetylases (HDACs), key epigenetic regulators of gene transcription, are involved in the development of the disease. EXPERIMENTAL APPROACHWe analysed HDAC regulation during cerulein-induced acute, chronic and autoimmune pancreatitis using different transgenic mouse models. The functional relevance of class I HDACs was tested with the selective inhibitor MS-275 in vivo upon pancreatitis induction and in vitro in activated macrophages and primary acinar cell explants. KEY RESULTSHDAC expression and activity were up-regulated in a time-dependent manner following induction of pancreatitis, with the highest abundance observed for class I HDACs. Class I HDAC inhibition did not prevent the initial acinar cell damage. However, it effectively reduced the infiltration of inflammatory cells, including macrophages and T cells, in both acute and chronic phases of the disease, and directly disrupted macrophage activation. In addition, MS-275 treatment reduced DNA damage in acinar cells and limited acinar de-differentiation into acinar-to-ductal metaplasia in a cell-autonomous manner by impeding the EGF receptor signalling axis. CONCLUSIONS AND IMPLICATIONSThese results demonstrate that class I HDACs are critically involved in the development of acute and chronic forms of pancreatitis and suggest that blockade of class I HDAC isoforms is a promising target to improve the outcome of the disease. IntroductionAbnormal activity of histone deacetylases (HDACs), a family of enzymes involved in the epigenetic control of gene transcription, has been implicated in the aetiology and development of several malignancies. However, recent evidence indicates that HDACs are also involved in the development of inflammatory diseases, highlighting the potential of targeting the activity of HDACs as a therapeutic approach to improve the outcome of rheumatoid arthritis (Choo et al., 2010(Choo et al., , 2013, neuritis (Zhang et al., 2010;Zhang and Schluesener, 2013), cholitis (Felice et al., 2015) and autoimmunity (Hancock et al., 2012).HDACs control the acetylation status of histone and non-histone proteins, thus regulating the expression of target genes (reviewed in Delcuve et al., 2012). The complexity of acetylation-based epigenetic regulation is reflected by the size of the mammalian HDAC family, composed of 11 zinc-dependent enzymes divided into three subfamilies (classes I, II and IV) and seven NAD-dependent enzymes in a fourth (sirtuin) subfamily (class III), with non-redundant functions.The function of HDAC subfamilies in the pathophysiology of pancreatitis, a highly debilitating inflammatory disease with a potentially lethal outcome, has not been thoroughly investigated. During pancreatitis, the ...

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“…Like other cancers, the development of pancreatic cancer is a multistep process with accumulation of genetic and epigenetic changes. Recent studies have revealed many pancreatic cancer-associated deregulated genes and signaling pathways (Chang et al, 2014;Ouaïssi et al, 2014), but the molecular mechanisms underlying the carcinogenesis, progression, and aggressiveness of the cancer have not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Propofol suppresses proliferation and invasion of pancreatic cancer cells by upregulating microRNA-133a expression

Zt¹,

Hy²,

Zheng³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Propofol is a commonly used intravenous anesthetic. We evaluated its effects on the behavior of human pancreatic cancer cells and the underlying molecular mechanisms. The effects of propofol on Panc-1 cell proliferation, apoptosis, and invasion were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, caspase-3 activity measurement, and Matrigel invasion assay. Quantitative polymerase chain reaction (qPCR) was used to assess microRNA-133a (miR-133a) expression. Anti-miR-133a was transfected into Panc-1 cells to assess the role of miR-133a in propofolinduced antitumor activity. Propofol significantly inhibited Panc-1 cell proliferation and invasion, and promoted apoptosis. Propofol also efficiently elevated miR-133a expression. Moreover, transfection of anti-miR-133a reversed the effects of propofol on the biological 7530 Z.T. Wang et al. ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (3): 7529-7537 (2015) behavior of Panc-1 cells. Propofol can effectively inhibit proliferation and invasion, and induce apoptosis of pancreatic cancer cells, at least partly through the upregulation of miR-133a expression.

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Further Characterization of HDAC and SIRT Gene Expression Patterns in Pancreatic Cancer and Their Relation to Disease Outcome

Cited by 34 publications

References 32 publications

Histone Deacetylase Inhibitor Trichostatin a Promotes the Apoptosis of Osteosarcoma Cells through p53 Signaling Pathway Activation

Histone Deacetylase Inhibitor Trichostatin a Promotes the Apoptosis of Osteosarcoma Cells through p53 Signaling Pathway Activation

Class I histone deacetylase inhibition improves pancreatitis outcome by limiting leukocyte recruitment and acinar‐to‐ductal metaplasia

Propofol suppresses proliferation and invasion of pancreatic cancer cells by upregulating microRNA-133a expression

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