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https://www.readbyqxmd.com/read/28322158/effect-and-mechanism-of-curcumin-on-ezh2-mir-101-regulatory-feedback-loop-in-multiple-myeloma
#1
Chuanqing Wu, Tuo Ruan, Weizhen Liu, Xiaojie Zhu, Juan Pan, Wen Lu, Chen Yan, Kaixiong Tao, Weikang Zhang, Chun Zhang
BACKGROUND: Multiple myeloma is the second most prevalent hematologic malignancy and thought to be incurable. Therefore, it's urgent to find new drugs for treatment. Some experiments have shown that curcumin might have great potential in treating multiple myeloma, while the mechanism is still unknown. EZH2 and SUZ12 are the core proteins in PRC2 and their expression are increased in various human cancers, including the poor prognostic multiple myeloma. Meanwhile, the regulation of miRNAs and EZH2 has been demonstrated in other cancer researches, like lung cancer, pancreatic cancer, leukemia and so on...
March 17, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28295484/who-2016-classification-changes-and-advancements-in-the-diagnosis-of-miscellaneous-primary-cns-tumours
#2
Felix Sahm, David E Reuss, Caterina Giannini
This short review highlights significant changes and recent findings incorporated to varying extent in the WHO 2016 definition of a variety of tumours, including peripheral nerve sheath tumours, meningiomas, mesenchymal non-meningothelial tumours, melanocytic tumours, lymphomas and histiocytic tumours, germ cell tumours and non-neuroendocrine pituitary tumours. Most notable classification changes include: adding "hybrid nerve sheath tumours" to the spectrum of benign nerve sheath tumours; an updated definition of atypical meningioma (WHO grade II), including cases with brain invasion; recognizing dural solitary fibrous tumour (SFT) and haemangiopericytoma (HPC) as a single tumour entity characterized by NAB2 and STAT6 gene fusions for which the term solitary SFT/HPC was chosen; recognizing that pituitary granular cell tumour, spindle cell oncocytoma, and pituicytoma all share nuclear expression of TTF-1, possibly representing a spectrum of a single nosological entity derived from posterior pituitary glial cells...
March 12, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/28229514/mutations-in-genes-encoding-polycomb-repressive-complex-2-subunits-cause-weaver-syndrome
#3
Eri Imagawa, Ken Higashimoto, Yasunari Sakai, Chikahiko Numakura, Nobuhiko Okamoto, Satoko Matsunaga, Akihide Ryo, Yoshinori Sato, Masafumi Sanefuji, Kenji Ihara, Yui Takada, Gen Nishimura, Hirotomo Saitsu, Takeshi Mizuguchi, Satoko Miyatake, Mitsuko Nakashima, Noriko Miyake, Hidenobu Soejima, Naomichi Matsumoto
Weaver syndrome is a rare congenital overgrowth disorder caused by heterozygous mutations in EZH2 (enhancer of zeste homolog 2) or EED (embryonic ectoderm development). EZH2 and EED are core components of the polycomb repressive complex 2 (PRC2), which possesses histone methyltransferase activity and catalyzes trimethylation of histone H3 at lysine 27. Here, we analyzed eight probands with clinically suspected Weaver syndrome by whole exome sequencing and identified three mutations: a 25.4-kb deletion partially involving EZH2 and CUL1 (individual 1), a missense mutation (c...
February 22, 2017: Human Mutation
https://www.readbyqxmd.com/read/28228691/overexpression-of-suppressor-of-zest-12-is-associated-with-cervical-node-metastasis-and-unfavorable-prognosis-in-tongue-squamous-cell-carcinoma
#4
Huijun Hu, Yi Wang, Zhongwu Li, Yumin Zhu, Wei Zhang, Dongmiao Wang, Tangyi Lin, Jianrong Yang, Yanling Wang, Jie Cheng
OBJECTIVE: Increased expression of suppressor of zest 12 (SUZ12), a core component of the polycomb repressive complex 2, contributes to human tumorigenesis and associates with patient prognosis. In the present study, we sought to investigate the expression of SUZ12 and its clinicopathological significance in primary tongue squamous cell carcinoma (TSCC). METHODS: The expression of SUZ12 protein was determined by immunohistochemistry in clinical samples from a retrospective cohort of 72 patients with primary TSCC who were treated at our institution from Jan...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28223321/a-non-canonical-function-of-ezh2-preserves-immune-homeostasis
#5
Ajithkumar Vasanthakumar, Dakang Xu, Aaron Tl Lun, Andrew J Kueh, Klaas Pjm van Gisbergen, Nadia Iannarella, Xiaofang Li, Liang Yu, Die Wang, Bryan Rg Williams, Stanley Cw Lee, Ian J Majewski, Dale I Godfrey, Gordon K Smyth, Warren S Alexander, Marco J Herold, Axel Kallies, Stephen L Nutt, Rhys S Allan
Enhancer of zeste 2 (Ezh2) mainly methylates lysine 27 of histone-H3 (H3K27me3) as part of the polycomb repressive complex 2 (PRC2) together with Suz12 and Eed. However, Ezh2 can also modify non-histone substrates, although it is unclear whether this mechanism has a role during development. Here, we present evidence for a chromatin-independent role of Ezh2 during T-cell development and immune homeostasis. T-cell-specific depletion of Ezh2 induces a pronounced expansion of natural killer T (NKT) cells, although Ezh2-deficient T cells maintain normal levels of H3K27me3...
February 21, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28213670/emerging-genotype-phenotype-relationships-in-patients-with-large-nf1-deletions
#6
REVIEW
Hildegard Kehrer-Sawatzki, Victor-Felix Mautner, David N Cooper
The most frequent recurring mutations in neurofibromatosis type 1 (NF1) are large deletions encompassing the NF1 gene and its flanking regions (NF1 microdeletions). The majority of these deletions encompass 1.4-Mb and are associated with the loss of 14 protein-coding genes and four microRNA genes. Patients with germline type-1 NF1 microdeletions frequently exhibit dysmorphic facial features, overgrowth/tall-for-age stature, significant delay in cognitive development, large hands and feet, hyperflexibility of joints and muscular hypotonia...
April 2017: Human Genetics
https://www.readbyqxmd.com/read/28192098/anti-leukemic-effects-of-hdaci-belinostat-and-hmti-3-deazaneplanocin-a-on-human-acute-promyelocytic-leukemia-cells
#7
Giedrė Valiulienė, Ieva Stirblytė, Monika Jasnauskaitė, Veronika Borutinskaitė, Rūta Navakauskienė
Development of acute myeloid leukemia is usually sustained by deregulated epigenome. Alterations in DNA methylation and histone modifications are common manifestations of the disease. Acute promyelocytic leukemia (APL) is not an exception. Therefore, drugs that target epigenetic processes suggest an appealing strategy for APL treatment. In this study we tested the anti-leukemic activity of histone deacetylase inhibitor (HDACi) Belinostat (PXD101, (2E)-N-Hydroxy-3-[3-(phenylsulfamoyl)phenyl]prop-2-enamide), and histone methyltransferase inhibitor (HMTi) 3-Deazaneplanocin A (DZNep, 5R-(4-amino-1H-imidazo[4,5-c]pyridin-1-yl)-3-(hydroxymethyl)-3-cyclopentene-1S,2R-diol) combined with retinoic acid (RA) in APL cells NB4 and HL-60...
February 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28135235/an-allosteric-prc2-inhibitor-targeting-the-h3k27me3-binding-pocket-of-eed
#8
Wei Qi, Kehao Zhao, Justin Gu, Ying Huang, Youzhen Wang, Hailong Zhang, Man Zhang, Jeff Zhang, Zhengtian Yu, Ling Li, Lin Teng, Shannon Chuai, Chao Zhang, Mengxi Zhao, HoMan Chan, Zijun Chen, Douglas Fang, Qi Fei, Leying Feng, Lijian Feng, Yuan Gao, Hui Ge, Xinjian Ge, Guobin Li, Andreas Lingel, Ying Lin, Yueqin Liu, Fangjun Luo, Minlong Shi, Long Wang, Zhaofu Wang, Yanyan Yu, Jue Zeng, Chenhui Zeng, Lijun Zhang, Qiong Zhang, Shaolian Zhou, Counde Oyang, Peter Atadja, En Li
Polycomb repressive complex 2 (PRC2) consists of three core subunits, EZH2, EED and SUZ12, and plays pivotal roles in transcriptional regulation. The catalytic subunit EZH2 methylates histone H3 lysine 27 (H3K27), and its activity is further enhanced by the binding of EED to trimethylated H3K27 (H3K27me3). Small-molecule inhibitors that compete with the cofactor S-adenosylmethionine (SAM) have been reported. Here we report the discovery of EED226, a potent and selective PRC2 inhibitor that directly binds to the H3K27me3 binding pocket of EED...
April 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28124441/confirmation-of-mutation-landscape-of-nf1-associated-malignant-peripheral-nerve-sheath-tumors
#9
Pierre Sohier, Armelle Luscan, Angharad Lloyd, Kevin Ashelford, Ingrid Laurendeau, Audrey Briand-Suleau, Dominique Vidaud, Nicolas Ortonne, Eric Pasmant, Meena Upadhyaya
The commonest tumors associated with neurofibromatosis type 1 (NF1) are benign peripheral nerve sheath tumors, called neurofibromas. Malignant transformation of neurofibromas into aggressive MPNSTs may occur with a poor patient prognosis. A cooperative role of SUZ12 or EED inactivation, along with NF1, TP53, and CDKN2A loss-of-function, has been proposed to drive progression to MPNSTs. An exome sequencing analysis of eight MPNSTs, one plexiform neurofibroma, and seven cutaneous neurofibromas was undertaken...
May 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28042859/a-novel-role-of-silibinin-as-a-putative-epigenetic-modulator-in-human-prostate-carcinoma
#10
Ioannis Anestopoulos, Aristeidis P Sfakianos, Rodrigo Franco, Katerina Chlichlia, Mihalis I Panayiotidis, David J Kroll, Aglaia Pappa
Silibinin, extracted from milk thistle (Silybum marianum L.), has exhibited considerable preclinical activity against prostate carcinoma. Its antitumor and chemopreventive activities have been associated with diverse effects on cell cycle, apoptosis, and receptor-dependent mitogenic signaling pathways. Here we hypothesized that silibinin's pleiotropic effects may reflect its interference with epigenetic mechanisms in human prostate cancer cells. More specifically, we have demonstrated that silibinin reduces gene expression levels of the Polycomb Repressive Complex 2 (PRC2) members Enhancer of Zeste Homolog 2 (EZH2), Suppressor of Zeste Homolog 12 (SUZ12), and Embryonic Ectoderm Development (EED) in DU145 and PC3 human prostate cancer cells, as evidenced by Real Time Polymerase Chain Reaction (RT-PCR)...
December 31, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28041882/lncrna-functional-networks-in-oligodendrocytes-reveal-stage-specific-myelination-control-by-an-lncol1-suz12-complex-in-the-cns
#11
Danyang He, Jincheng Wang, Yulan Lu, Yaqi Deng, Chuntao Zhao, Lingli Xu, Yinhuai Chen, Yueh-Chiang Hu, Wenhao Zhou, Q Richard Lu
Long noncoding RNAs (lncRNAs) are emerging as important regulators of cellular functions, but their roles in oligodendrocyte myelination remain undefined. Through de novo transcriptome reconstruction, we establish dynamic expression profiles of lncRNAs at different stages of oligodendrocyte development and uncover a cohort of stage-specific oligodendrocyte-restricted lncRNAs, including a conserved chromatin-associated lncOL1. Co-expression network analyses further define the association of distinct oligodendrocyte-expressing lncRNA clusters with protein-coding genes and predict lncRNA functions in oligodendrocyte myelination...
January 18, 2017: Neuron
https://www.readbyqxmd.com/read/28002623/comprehensive-screening-for-med12-mutations-in-gynecological-mesenchymal-tumors-identified-morphologically-distinctive-mixed-epithelial-and-stromal-tumors
#12
Chang-Tsu Yuan, Wen-Chih Huang, Cheng-Han Lee, Ming-Chieh Lin, Chen-Hui Lee, Yu-Chien Kao, Hsuan-Ying Huang, Kuan-Ting Kuo, Jen-Chieh Lee
BACKGROUND: MED12 exon 2 mutations have been identified in most uterine leiomyomas and mammary fibroepithelial tumors. MED12 has not been genotyped in most other gynecological mesenchymal tumors. DESIGN: 68 uncommon gynecological mesenchymal tumors were genotyped for MED12 exon 2, including 27 müllerian adenosarcomas (including 3 tentatively diagnosed as "variant adenosarcomas"), 6 cellular angiofibromas, 6 aggressive angiomyxomas, 5 angiomyofibroblastomas, 5 superficial myofibroblastomas, 5 atypical polypoid adenomyomas, and 14 endometrial stromal sarcomas...
December 21, 2016: Histopathology
https://www.readbyqxmd.com/read/27902735/role-of-hepatic-specific-transcription-factors-and-polycomb-repressive-complex-2-during-induction-of-fibroblasts-to-hepatic-fate
#13
Shima Rastegar-Pouyani, Niusha Khazaei, Ping Wee, Abdulshakour Mohammadnia, Moein Yaqubi
Direct reprogramming using defined sets of transcription factors (TFs) is a recent strategy for generating induced hepatocytes (iHeps) from fibroblasts for use in regenerative medicine and drug development. Comprehensive studies detailing the regulatory role of TFs during this reprogramming process could help increase its efficiency. This study aimed to find the TFs with the greatest influences on the generation of iHeps from fibroblasts, and to further understand their roles in the regulation of the gene expression program...
2016: PloS One
https://www.readbyqxmd.com/read/27845897/the-jazf1-suz12-fusion-protein-disrupts-prc2-complexes-and-impairs-chromatin-repression-during-human-endometrial-stromal-tumorogenesis
#14
Xianyong Ma, Jinglan Wang, Jianhui Wang, Charles X Ma, Xiaobin Gao, Vytas Patriub, Jeffrey L Sklar
The Polycomb repressive complex 2 (PRC2), which contains three core proteins EZH2, EED and SUZ12, controls chromatin compaction and transcription repression through trimethylation of lysine 27 on histone 3. The (7;17)(p15;q21) chromosomal translocation present in most cases of endometrial stromal sarcomas (ESSs) results in the in-frame fusion of the JAZF1 and SUZ12 genes. We have investigated whether and how the fusion protein JAZF1-SUZ12 functionally alters PRC2. We found that the fusion protein exists at high levels in ESS containing the t(7;17)...
November 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27823568/pharmacological-histone-deacetylation-segregates-distinct-regulators-of-transcription
#15
Haloom Rafehi, Tom C Karagiannis, Assam El-Osta
INTRODUCTION: Histone deacetylase (HDAC) enzymes control the acetylation status of transcription factors that regulate chromatin structure and gene function. The transcriptional regulatory factors that distinguish histone acetylation and deacetylation patterns by pharmacological HDAC inhibition (HDACi) have been studied. METHODS: We analysed sequencing datasets derived from human aortic endothelial cells (HAECs) stimulated with the HDAC inhibitors, Trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA)...
November 4, 2016: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/27818691/osteogenic-differentiation-of-human-amniotic-fluid-mesenchymal-stem-cells-is-determined-by-epigenetic-changes
#16
Monika Glemžaitė, Rūta Navakauskienė
Osteogenic differentiation of human amniotic fluid derived mesenchymal stem cells (AF-MSCs) has been widely studied in vitro and in vivo as a potential tool for regenerative medicine and tissue engineering. While most of the studies analyze changes in transcriptional profile during differentiation to date there is not much information regarding epigenetic changes in AF-MSCs during differentiation. The aim of our study was to evaluate epigenetic changes during osteogenic differentiation of AF-MS cells. Isolated AF-MSCs were characterized morphologically and osteogenic differentiation was confirmed by cell staining and determining expression of alkaline phosphatase and osteopontin by RT-qPCR...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27803714/senescence-associated-molecular-and-epigenetic-alterations-in-mesenchymal-stem-cell-cultures-from-amniotic-fluid-of-normal-and-fetus-affected-pregnancy
#17
Jūratė Savickienė, Sandra Baronaitė, Aistė Zentelytė, Gražina Treigytė, Rūta Navakauskienė
Human amniotic-fluid-derived mesenchymal stem cells (AF-MSCs) are interesting for their multilineage differentiation potential and wide range of therapeutic applications due to the ease of culture expansion. However, MSCs undergo replicative senescence. So far, the molecular mechanisms that underlie fetal diseases and cell senescence are still poorly understood. Here, we analyzed senescence-associated morphologic, molecular, and epigenetic characteristics during propagation of MSCs derived from AF of normal and fetus-affected pregnancy...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27783956/highly-efficient-genome-editing-of-murine-and-human-hematopoietic-progenitor-cells-by-crispr-cas9
#18
Michael C Gundry, Lorenzo Brunetti, Angelique Lin, Allison E Mayle, Ayumi Kitano, Dimitrios Wagner, Joanne I Hsu, Kevin A Hoegenauer, Cliona M Rooney, Margaret A Goodell, Daisuke Nakada
Our understanding of the mechanisms that regulate hematopoietic stem/progenitor cells (HSPCs) has been advanced by the ability to genetically manipulate mice; however, germline modification is time consuming and expensive. Here, we describe fast, efficient, and cost-effective methods to directly modify the genomes of mouse and human HSPCs using the CRISPR/Cas9 system. Using plasmid and virus-free delivery of guide RNAs alone into Cas9-expressing HSPCs or Cas9-guide RNA ribonucleoprotein (RNP) complexes into wild-type cells, we have achieved extremely efficient gene disruption in primary HSPCs from mouse (>60%) and human (∼75%)...
October 25, 2016: Cell Reports
https://www.readbyqxmd.com/read/27738815/-new-features-in-the-2014-who-classification-of-uterine-neoplasms
#19
S F Lax
The 2014 World Health Organization (WHO) classification of uterine tumors revealed simplification of the classification by fusion of several entities and the introduction of novel entities. Among the multitude of alterations, the following are named: a simplified classification for precursor lesions of endometrial carcinoma now distinguishes between hyperplasia without atypia and atypical hyperplasia, the latter also known as endometrioid intraepithelial neoplasia (EIN). For endometrial carcinoma a differentiation is made between type 1 (endometrioid carcinoma with variants and mucinous carcinoma) and type 2 (serous and clear cell carcinoma)...
November 2016: Der Pathologe
https://www.readbyqxmd.com/read/27659532/promoter-methylation-of-pcdh10-by-hotair-regulates-the-progression-of-gastrointestinal-stromal-tumors
#20
Na Keum Lee, Jung Hwa Lee, Won Kyu Kim, Seongju Yun, Young Hoon Youn, Chan Hyuk Park, Yun Young Choi, Hogeun Kim, Sang Kil Lee
HOTAIR, a long non-coding RNA (lncRNA), plays a crucial role in tumor initiation and metastasis by interacting with the PRC2 complex and the modulation of its target genes. The role of HOTAIR in gastrointestinal stromal tumors (GISTs) is remains unclear. Herein we investigate the mechanism of HOTAIR in the genesis and promotion of GISTs. The expression of HOTAIR was found to be higher in surgically resected high-risk GISTs than that in low- and intermediate-risk GISTs. Using GIST-T1 and GIST882 cells, we demonstrated that HOTAIR repressed apoptosis, was associated with cell cycle progression, and controlled the invasion and migration of GIST cells...
November 15, 2016: Oncotarget
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