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Phf8

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https://www.readbyqxmd.com/read/28991226/lsd1-promotes-s-phase-entry-and-tumorigenesis-via-chromatin-co-occupation-with-e2f1-and-selective-h3k9-demethylation
#1
Y He, Y Zhao, L Wang, L R Bohrer, Y Pan, L Wang, H Huang
Histone H3 lysine-9 (H3K9) methylation is essential for retinoblastoma protein (RB)-mediated heterochromatin formation, epigenetic silencing of S-phase genes and permanent cell cycle arrest or cellular senescence. Besides as an H3K4 demethylase, lysine-specific demethylase-1 (LSD1) has been shown to promote H3K9 demethylation. However, it is unexplored whether LSD1 has a causal role in regulating cell cycle entry and senescence. Here we demonstrate that genetic depletion or pharmacological inhibition of LSD1 triggers G1 arrest and cellular senescence...
October 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28765946/histone-demethylase-phf8-accelerates-the-progression-of-colorectal-cancer-and-can-be-regulated-by-mir-488-in%C3%A2-vitro
#2
Yao Lv, Yan Shi, Quanli Han, Guanghai Dai
Plant homeo domain finger protein 8 (PHF8), as an oncogene, has been highlighted in cancer development and progression. However, its clinical significance and underlying molecular mechanisms in colorectal cancer (CRC) remain to be fully elucidated. In the present study, the role of PHF8 in the progression of CRC was investigated. The mRNA and protein levels of PHF8 in tissues from patients with CRC and cell lines were detected using the reverse transcription-quantitative polymerase chain reaction and western blotting, respectively...
October 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28734980/histone-demethylase-phf8-regulates-hypoxia-signaling-through-hif1%C3%AE-and-h3k4me3
#3
Peterson Kariuki Maina, Peng Shao, Xiongfei Jia, Qi Liu, Shaikamjad Umesalma, Maximo Marin, Donald Long, Samantha Concepción-Román, Hank Heng Qi
Hypoxia through transcription factor HIF1α plays a critical role in cancer development. In prostate cancer, HIF1α interplays with androgen receptor (AR) to contribute to the progression of this disease to its lethal form-castration-resistant prostate cancer (CRPC). Hypoxia upregulates several epigenetic factors including histone demethylase KDM3A which is a critical co-factor of HIF1α. However, how histone demethylases regulate hypoxia signaling is not fully understood. Here, we report that histone demethylase PHF8 plays an essential role in hypoxia signaling...
September 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28592245/in-silico-identification-of-potential-key-regulatory-factors-in-smoking-induced-lung-cancer
#4
Salem A El-Aarag, Amal Mahmoud, Medhat H Hashem, Hatem Abd Elkader, Alaa E Hemeida, Mahmoud ElHefnawi
BACKGROUND: Lung cancer is a leading cause of cancer-related death worldwide and is the most commonly diagnosed cancer. Like other cancers, it is a complex and highly heterogeneous disease involving multiple signaling pathways. Identifying potential therapeutic targets is critical for the development of effective treatment strategies. METHODS: We used a systems biology approach to identify potential key regulatory factors in smoking-induced lung cancer. We first identified genes that were differentially expressed between smokers with normal lungs and those with cancerous lungs, then integrated these differentially expressed genes (DEGs) with data from a protein-protein interaction database to build a network model with functional modules for pathway analysis...
June 7, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28485378/phf8-loss-confers-resistance-to-depression-like-and-anxiety-like-behaviors-in-mice
#5
Ryan M Walsh, Erica Y Shen, Rosemary C Bagot, Anthony Anselmo, Yan Jiang, Behnam Javidfar, Gregory J Wojtkiewicz, Jennifer Cloutier, John W Chen, Ruslan Sadreyev, Eric J Nestler, Schahram Akbarian, Konrad Hochedlinger
PHF8 is a histone demethylase with specificity for repressive modifications. While mutations of PHF8 have been associated with cognitive defects and cleft lip/palate, its role in mammalian development and physiology remains unexplored. Here, we have generated a Phf8 knockout allele in mice to examine the consequences of Phf8 loss for development and behaviour. Phf8 deficient mice neither display obvious developmental defects nor signs of cognitive impairment. However, we report a striking resiliency to stress-induced anxiety- and depression-like behaviour on loss of Phf8...
May 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28430394/structure-based-design-of-a-new-scaffold-for-cell-penetrating-peptidic-inhibitors-of-the-histone-demethylase-phf8
#6
Jerzy Dorosz, Lars Olsen, Signe Teuber Seger, Cornelia Steinhauer, Giorgos Bouras, Charlotte Helgstrand, Anders Wiuf, Michael Gajhede
The histone demethylase PHF8 catalyzes demethylation of mono- and di-methylated Lys9 on histone H3 (H3K9me1/2), and is a transcriptional activator involved in the development and cancer. Affinity and specificity of PHF8 towards H3K9me2 is affected by interaction with both the catalytic domain and a PHD reader domain. The latter specifically recognizes tri-methylated Ly4 on histone H3. A fragment of the histone H3 tail with tri-methylated Lys4 was used as a template for the structure-based design of a cyclic, cell-penetrating peptide that exhibits micromolar binding affinity to PHF8 in biochemical assays...
July 18, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28401003/histone-demethylase-phf8-promotes-progression-and-metastasis-of-gastric-cancer
#7
Shuyan Li, Ao Sun, Xiuming Liang, Lin Ma, Li Shen, Tongyu Li, Lixin Zheng, Wenjing Shang, Wei Zhao, Jihui Jia
Histone demethylase plant homeodomain (PHD) finger protein 8 (PHF8) has been implicated in tumor development and malignant progression in various types of cancers. However, its potential roles in gastric cancer (GC) have not been explored. In this report, we show that PHF8 expression is upregulated in GC tissues, and the enhanced PHF8 level indicates a poor prognosis of GC patients. PHF8 knockdown reduces proliferation and metastasis of GC cells, while PHF8 overexpression has the opposite effects. Mechanistically, PHF8 interacts with β-catenin, and binds to the promoter region of vimentin, leading to the promotion of vimentin transcription...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28126843/jmjd-1-2-phf8-controls-axon-guidance-by-regulating-hedgehog-like-signaling
#8
Alba Redo Riveiro, Luca Mariani, Emily Malmberg, Pier Giorgio Amendola, Juhani Peltonen, Garry Wong, Anna Elisabetta Salcini
Components of the KDM7 family of histone demethylases are implicated in neuronal development and one member, PHF8, is often found to be mutated in cases of X-linked mental retardation. However, how PHF8 regulates neurodevelopmental processes and contributes to the disease is still largely unknown. Here, we show that the catalytic activity of a PHF8 homolog in Caenorhabditis elegans, JMJD-1.2, is required non-cell-autonomously for proper axon guidance. Loss of JMJD-1.2 dysregulates transcription of the Hedgehog-related genes wrt-8 and grl-16, the overexpression of which is sufficient to induce the axonal defects...
March 1, 2017: Development
https://www.readbyqxmd.com/read/28100697/the-histone-demethylase-phf8-is-a-molecular-safeguard-of-the-ifn%C3%AE-response
#9
Elena Asensio-Juan, Raquel Fueyo, Stella Pappa, Simona Iacobucci, Carmen Badosa, Sergi Lois, Miriam Balada, Laia Bosch-Presegué, Alex Vaquero, Sara Gutiérrez, Carme Caelles, Carme Gallego, Xavier de la Cruz, Marian A Martínez-Balbás
A precise immune response is essential for cellular homeostasis and animal survival. The paramount importance of its control is reflected by the fact that its non-specific activation leads to inflammatory events that ultimately contribute to the appearance of many chronic diseases. However, the molecular mechanisms preventing non-specific activation and allowing a quick response upon signal activation are not yet fully understood. In this paper we uncover a new function of PHF8 blocking signal independent activation of immune gene promoters...
April 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27991916/the-hif-phf8-ar-axis-promotes-prostate-cancer-progression
#10
D Tong, Q Liu, G Liu, W Yuan, L Wang, Y Guo, W Lan, D Zhang, S Dong, Y Wang, H Xiao, J Mu, C Mao, J Wong, J Jiang
Recent studies provide strong evidence that the androgen receptor (AR) signaling pathway remains active in castration-resistant prostate cancer (CRPC). However, the underlying mechanisms are not well understood. In this study, we demonstrate that plant homeo domain finger protein 8 (PHF8 )interacts with and functions as an essential histone demethylase activity-dependent AR coactivator. Furthermore, we demonstrate that the expression of PHF8 is induced by hypoxia in various prostate cancer cell lines. Knockdown of either hypoxia-inducible factor HIF2α or HIF1α almost completely abolished hypoxia-induced PHF8 expression...
December 19, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27899639/histone-demethylase-phf8-promotes-epithelial-to-mesenchymal-transition-and-breast-tumorigenesis
#11
Peng Shao, Qi Liu, Peterson Kariuki Maina, Jiayue Cui, Thomas B Bair, Tiandao Li, Shaikamjad Umesalma, Weizhou Zhang, Hank Heng Qi
Histone demethylase PHF8 is upregulated and plays oncogenic roles in various cancers; however, the mechanisms underlying its dysregulation and functions in carcinogenesis remain obscure. Here, we report the novel functions of PHF8 in EMT (epithelial to mesenchymal transition) and breast cancer development. Genome-wide gene expression analysis revealed that PHF8 overexpression induces an EMT-like process, including the upregulation of SNAI1 and ZEB1. PHF8 demethylates H3K9me1, H3K9me2 and sustains H3K4me3 to prime the transcriptional activation of SNAI1 by TGF-β signaling...
February 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27689328/c-myc-drives-histone-demethylase-phf8-during-neuroendocrine-differentiation-and-in-castration-resistant-prostate-cancer
#12
Peterson Kariuki Maina, Peng Shao, Qi Liu, Ladan Fazli, Scott Tyler, Moman Nasir, Xuesen Dong, Hank Heng Qi
Epigenetic factors play critical roles in prostate cancer (PCa) development. However, how they contribute to neuroendocrine differentiation (NED) and castration-resistant PCa (CRPC) is not fully understood. Using bioinformatics and biochemical approaches to analyze cell-based models of NED and CRPC, we found a cluster of epigenetic factors whose expression is downregulated during NED and upregulated in CRPC (i.e. follow a Down-Up pattern). Two histone demethylases within this cluster, PHF8 and KDM3A, are post-transcriptionally regulated by c-MYC through miR-22, which targets both PHF8 and KDM3A...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27183383/stabilization-of-histone-demethylase-phf8-by-usp7-promotes-breast-carcinogenesis
#13
Qian Wang, Shuai Ma, Nan Song, Xin Li, Ling Liu, Shangda Yang, Xiang Ding, Lin Shan, Xing Zhou, Dongxue Su, Yue Wang, Qi Zhang, Xinhua Liu, Na Yu, Kai Zhang, Yongfeng Shang, Zhi Yao, Lei Shi
The histone demethylase PHF8 has been implicated in multiple pathological disorders, including X-linked mental retardation and tumorigenesis. However, it is not clear how the abundance and function of PHF8 are regulated. Here, we report that PHF8 physically associates with the deubiquitinase USP7. Specifically, we demonstrated that USP7 promotes deubiquitination and stabilization of PHF8, leading to the upregulation of a group of genes, including cyclin A2, that are critical for cell growth and proliferation...
June 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27133168/two-conserved-histone-demethylases-regulate-mitochondrial-stress-induced-longevity
#14
Carsten Merkwirth, Virginija Jovaisaite, Jenni Durieux, Olli Matilainen, Sabine D Jordan, Pedro M Quiros, Kristan K Steffen, Evan G Williams, Laurent Mouchiroud, Sarah U Tronnes, Virginia Murillo, Suzanne C Wolff, Reuben J Shaw, Johan Auwerx, Andrew Dillin
Across eukaryotic species, mild mitochondrial stress can have beneficial effects on the lifespan of organisms. Mitochondrial dysfunction activates an unfolded protein response (UPR(mt)), a stress signaling mechanism designed to ensure mitochondrial homeostasis. Perturbation of mitochondria during larval development in C. elegans not only delays aging but also maintains UPR(mt) signaling, suggesting an epigenetic mechanism that modulates both longevity and mitochondrial proteostasis throughout life. We identify the conserved histone lysine demethylases jmjd-1...
May 19, 2016: Cell
https://www.readbyqxmd.com/read/27112199/proteomic-dissection-of-lps-inducible-phf8-dependent-secretome-reveals-novel-roles-of-phf8-in-tlr4-induced-acute-inflammation-and-t-cell-proliferation
#15
Özgün Erdoğan, Ling Xie, Li Wang, Bing Wu, Qing Kong, Yisong Wan, Xian Chen
Endotoxin (LPS)-induced changes in histone lysine methylation contribute to the gene-specific transcription for control of inflammation. Still unidentified are the chromatin regulators that drive the transition from a transcriptional-repressive to a transcriptional-active chromatin state of pro-inflammatory genes. Here, using combined approaches to analyze LPS-induced changes in both gene-specific transcription and protein secretion to the extracellular compartment, we characterize novel functions of the lysine demethylase PHF8 as a pro-inflammatory, gene-specific chromatin regulator...
April 26, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27014810/-the-pilot-study-on-the-expression-of-phf8-h3k9me2-bdnf-and-ltp-in-the-hippocampus-of-rats-exposed-to-aluminum
#16
Zhaoyang Li, Pan Kang, H uifang Zhang, Xiaohan Nie, Yuzhou Yuan, Qiao Niu
OBJECTIVE: In this research, we have observed changes of PHF8、H3K9me2、BDNF, and their regulatory roles in changing the amplitude value of LTP in hippocampus due to aluminum exposure so that we can discuss the impact on the learning and memory that caused by chronic aluminum exposure. METHODS: Forty healthy SPF grade SD male rats were randomly divided into four groups by weight, including control group and low, medium, high dose aluminum exposed group, each group had 10 rats...
January 2016: Chinese Journal of Industrial Hygiene and Occupational Diseases
https://www.readbyqxmd.com/read/26866517/plant-homeo-domain-finger-protein-8-regulates-mesodermal-and-cardiac-differentiation-of-embryonic-stem-cells-through-mediating-the-histone-demethylation-of-pmaip1
#17
Yan Tang, Ya-Zhen Hong, Hua-Jun Bai, Qiang Wu, Charlie Degui Chen, Jing-Yu Lang, Kenneth R Boheler, Huang-Tian Yang
Histone demethylases have emerged as key regulators of biological processes. The H3K9me2 demethylase plant homeo domain finger protein 8(PHF8), for example, is involved in neuronal differentiation, but its potential function in the differentiation of embryonic stem cells (ESCs) to cardiomyocytes is poorly understood. Here, we explored the role of PHF8 during mesodermal and cardiac lineage commitment of mouse ESCs (mESCs). Using a phf8 knockout (ph8(-/Y) ) model, we found that deletion of phf8 in ESCs did not affect self-renewal, proliferation or early ectodermal/endodermal differentiation, but it did promote the mesodermal lineage commitment with the enhanced cardiomyocyte differentiation...
June 2016: Stem Cells
https://www.readbyqxmd.com/read/26464965/a-neuronal-activity-dependent-dual-function-chromatin-modifying-complex-regulates-arc-expression-1-2-3
#18
Nicodemus E Oey, How Wing Leung, Rajaram Ezhilarasan, Lei Zhou, Roger W Beuerman, Hendrika M A VanDongen, Antonius M J VanDongen
Chromatin modification is an important epigenetic mechanism underlying neuroplasticity. Histone methylation and acetylation have both been shown to modulate gene expression, but the machinery responsible for mediating these changes in neurons has remained elusive. Here we identify a chromatin-modifying complex containing the histone demethylase PHF8 and the acetyltransferase TIP60 as a key regulator of the activity-induced expression of Arc, an important mediator of synaptic plasticity. Clinically, mutations in PHF8 cause X-linked mental retardation while TIP60 has been implicated in the pathogenesis of Alzheimer's disease...
January 2015: ENeuro
https://www.readbyqxmd.com/read/26461474/mir137-is-an-androgen-regulated-repressor-of-an-extended-network-of-transcriptional-coregulators
#19
Emeli M Nilsson, Kristian B Laursen, Jonathan Whitchurch, Andrew McWilliam, Niels Ødum, Jenny L Persson, David M Heery, Lorraine J Gudas, Nigel P Mongan
Androgens and the androgen receptor (AR) play crucial roles in male development and the pathogenesis and progression of prostate cancer (PCa). The AR functions as a ligand dependent transcription factor which recruits multiple enzymatically distinct epigenetic coregulators to facilitate transcriptional regulation in response to androgens. Over-expression of AR coregulators is implicated in cancer. We have shown that over-expression of KDM1A, an AR coregulator, contributes to PCa recurrence by promoting VEGFA expression...
November 3, 2015: Oncotarget
https://www.readbyqxmd.com/read/26309412/the-histone-demethylase-phf8-promotes-prostate-cancer-cell-growth-by-activating-the-oncomir-mir-125b
#20
Qiang Ma, Zhuo Chen, Guojin Jia, Xueqiang Lu, Xuefeng Xie, Wei Jin
AIMS: Prostate cancer (PCa) is the most frequently diagnosed malignancy in men. However, the underlying mechanism is not fully understood. In this study, we aim to research the molecular mechanisms underlying the initiation and progression of PCa. RESULTS: Plant homeodomain finger protein 8 (PHF8) is upregulated in human PCa tissues and cell lines. PHF8 knockdown attenuates growth and cellular transformation of PCa cells. PHF8 depletion induces PCa cell apoptosis by activating proapoptotic proteins and inactivating antiapoptotic proteins...
2015: OncoTargets and Therapy
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