Role of histone deacetylase expression in intrahepatic cholangiocarcinoma

Tumor development and progression is the consequence of genetic as well as epigenetic alterations of the cell. As part of the epigenetic regulatory system, histone acetyltransferases (HATs) and deacetylases (HDACs) drive the modification of histone as well as non-histone proteins. Derailed acetylation-mediated gene expression in cancer due to a delicate imbalance in HDAC expression can be reversed by histone deacetylase inhibitors (HDACi). Histone deacetylase inhibitors have far-reaching anticancer activities that include the induction of cell cycle arrest, the inhibition of angiogenesis, immunomodulatory responses, the inhibition of stress responses, increased generation of oxidative stress, activation of apoptosis, autophagy eliciting cell death, and even the regulation of non-coding RNA expression in malignant tumor cells. However, it remains an ongoing issue how tumor cells determine to respond to HDACi treatment by preferentially undergoing apoptosis or autophagy. In this review, we summarize HDACi-mediated mechanisms of action, particularly with respect to the induction of cell death. There is a keen interest in assessing suitable molecular factors allowing a prognosis of HDACi-mediated treatment. Addressing the results of our recent study, we highlight the role of p53 as a molecular switch driving HDACi-mediated cellular responses towards one of both types of cell death. These findings underline the importance to determine the mutational status of p53 for an effective outcome in HDACi-mediated tumor therapy.

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The Rpd3-Sin3 Histone Deacetylase Regulates Replication Timing and Enables Intra-S Origin Control in Saccharomyces cerevisiae

Molecular and Cellular Biology ◽

10.1128/mcb.24.11.4769-4780.2004 ◽

2004 ◽

Vol 24 (11) ◽

pp. 4769-4780 ◽

Cited By ~ 108

Author(s):

Jennifer G. Aparicio ◽

Christopher J. Viggiani ◽

Daniel G. Gibson ◽

Oscar M. Aparicio

Keyword(s):

Saccharomyces Cerevisiae ◽

Histone Deacetylase ◽

Transcriptional Repression ◽

Replication Timing ◽

Histone Deacetylation ◽

Origin Firing ◽

Replication Checkpoint ◽

Genome Transcription ◽

Late Origin

ABSTRACT The replication of eukaryotic genomes follows a temporally staged program, in which late origin firing often occurs within domains of altered chromatin structure(s) and silenced genes. Histone deacetylation functions in gene silencing in some late-replicating regions, prompting an investigation of the role of histone deacetylation in replication timing control in Saccharomyces cerevisiae. Deletion of the histone deacetylase Rpd3 or its interacting partner Sin3 caused early activation of late origins at internal chromosomal loci but did not alter the initiation timing of early origins or a late-firing, telomere-proximal origin. By delaying initiation relative to the earliest origins, Rpd3 enables regulation of late origins by the intra-S replication checkpoint. RPD3 deletion suppresses the slow S phase of clb5Δ cells by enabling late origins to fire earlier, suggesting that Rpd3 modulates the initiation timing of many origins throughout the genome. Examination of factors such as Ume6 that function together with Rpd3 in transcriptional repression indicates that Rpd3 regulates origin initiation timing independently of its role in transcriptional repression. This supports growing evidence that for much of the S. cerevisiae genome transcription and replication timing are not linked.

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Role of Histone Deacetylase Inhibitors in Relapsed Refractory Multiple Myeloma: A Focus on Vorinostat and Panobinostat

Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy ◽

10.1002/phar.1671 ◽

2015 ◽

Vol 35 (12) ◽

pp. 1173-1188 ◽

Cited By ~ 32

Author(s):

Salma Afifi ◽

Angela Michael ◽

Mahshid Azimi ◽

Mabel Rodriguez ◽

Nikoletta Lendvai ◽

...

Keyword(s):

Multiple Myeloma ◽

Histone Deacetylase ◽

Histone Deacetylase Inhibitors ◽

Refractory Multiple Myeloma

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The role of sarcopenia in patients with intrahepatic cholangiocarcinoma: Prognostic marker or hyped parameter?

Liver International ◽

10.1111/liv.14132 ◽

2019 ◽

Vol 39 (7) ◽

pp. 1307-1314 ◽

Cited By ~ 5

Author(s):

Felix Hahn ◽

Lukas Müller ◽

Fabian Stöhr ◽

Aline Mähringer‐Kunz ◽

Sebastian Schotten ◽

...

Keyword(s):

Prognostic Marker ◽

Intrahepatic Cholangiocarcinoma

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The prognostic role of lymphovascular invasion and lymph node metastasis in perihilar and intrahepatic cholangiocarcinoma

HPB ◽

10.1016/j.hpb.2020.04.160 ◽

2020 ◽

Vol 22 ◽

pp. S264-S265

Author(s):

J. Bednarsch ◽

Z. Czigany ◽

I. Amygdalos ◽

D Morales Santana ◽

M. Den Dulk ◽

...

Keyword(s):

Lymph Node ◽

Lymph Node Metastasis ◽

Intrahepatic Cholangiocarcinoma ◽

Lymphovascular Invasion ◽

Prognostic Role ◽

Node Metastasis

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The role of histone deacetylase 7 (HDAC7) in cancer cell proliferation: regulation on c-Myc

Journal of Molecular Medicine ◽

10.1007/s00109-010-0701-7 ◽

2010 ◽

Vol 89 (3) ◽

pp. 279-289 ◽

Cited By ~ 29

Author(s):

Caihua Zhu ◽

Qin Chen ◽

Zuoquan Xie ◽

Jing Ai ◽

Linjiang Tong ◽

...

Keyword(s):

Cell Proliferation ◽

Histone Deacetylase ◽

Cancer Cell ◽

Cancer Cell Proliferation ◽

Proliferation Regulation

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Role of Erythromycin-Regulated Histone Deacetylase-2 in Benign Tracheal Stenosis

Canadian Respiratory Journal ◽

10.1155/2020/4213807 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Zhenjie Huang ◽

Peng Wei ◽

Luoman Gan ◽

Tonghua Zeng ◽

Caicheng Qin ◽

...

Keyword(s):

Histone Deacetylase ◽

Tracheal Stenosis ◽

Type I Collagen ◽

Rabbit Model ◽

Immunohistochemical Method ◽

Type Iii Collagen ◽

Type I ◽

Histone Deacetylase 2 ◽

Budesonide Group

Objective. This study aims to explore the role of erythromycin-regulated histone deacetylase-2 in benign tracheal stenosis. Methods. The rabbit model of tracheal stenosis was established. The rabbits were randomly divided into 8 groups. Histone deacetylase-2 (HDAC2) expression was detected by immunofluorescence. The expression of type I collagen and type III collagen was detected by immunohistochemical method. The expression of TGF-β1, VEGF and IL-8 in serum and alveolar lavage fluid was detected by ELISA. The expression of HDAC2, TGF-β1, VEGF and IL-8 in bronchi of each group was detected by Western blotting method. Results. In Erythromycin (ERY) group, ERY + Budesonide group, ERY + Vorinostat group and ERY + Budesonide + Vorinostat group, the degree of bronchial stenosis was alleviated, and the mucosal epithelium was still slightly proliferated. The effect of ERY combined with other drugs was more obvious. The HDAC2 protein expression increased significantly in ERY group, ERY + Budesonide group and ERY + Budesonide + Vorinostat group and decreased significantly in Vorinostat group, the expression of collagen I and III decreased significantly in ERY group, ERY + Budesonide group and ERY + Budesonide + Vorinostat group (P<0.05). The TGF-β1, IL-8 and VEGF levels decreased significantly in ERY group, ERY + Budesonide group, ERY + Vorinostat group and ERY + Budesonide + Vorinostat group (P<0.05). Conclusions. Erythromycin inhibited inflammation and excessive proliferation of granulation tissue after tracheobronchial mucosal injury by up-regulating the expression of HDAC2, it promoted wound healing and alleviated tracheobronchial stenosis. When combined with budesonide, penicillin and other glucocorticoids and antibiotics, it had a good synergistic effect. However, vorinostat could attenuate erythromycin’s effect by down-regulating the expression of HDAC2. It may have good clinical application prospects in the treatment of tracheal stenosis.

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