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https://www.readbyqxmd.com/read/28641467/green-tea-polyphenol-egcg-causes-anti-cancerous-epigenetic-modulations-in-acute-promyelocytic-leukemia-cells
#1
Veronika Borutinskaitė, Aida Virkšaitė, Giedrė Gudelytė, Rūta Navakauskienė
Green tea (Camellia sinensis) catechin epigallocatechin-3-gallate (EGCG) has been shown to possess diverse anti-cancerous properties. We demonstrated EGCG ability to inhibit acute promyelocytic leukemia (APL) cell proliferation and cause apoptosis. In addition, quantitative real-time polymerase chain reaction (RT-qPCR) analysis revealed elevated expression of genes associated with cell cycle arrest and differentiation (p27, PCAF, C/EBPα, and C/EBPɛ). Furthermore, EGCG caused anti-cancerous epigenetic changes: downregulation of epigenetic modifiers DNMT1, HDAC1, HDAC2, and G9a was observed by RT-qPCR analysis...
June 22, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28618952/microrna-105-inhibits-human-glioma-cell-malignancy-by-directly-targeting-suz12
#2
Jie Zhang, Weining Wu, Shuo Xu, Jian Zhang, Jiale Zhang, Qun Yu, Yuanyuan Jiao, Yingyi Wang, Ailin Lu, Yongping You, Junxia Zhang, Xiaoming Lu
Glioma accounts for the majority of primary malignant brain tumors in adults and is highly aggressive. Although various therapeutic approaches have been applied, outcomes of glioma treatment remain poor. MicroRNAs are a class of small noncoding RNAs that function as regulators of gene expression. Accumulating evidence shows that microRNAs are associated with tumorigenesis and tumor progression. In this study, we found that miR-105 is significantly downregulated in glioma tissues and glioma cell lines. We identified suppressor of Zeste 12 homolog as a novel direct target of miR-105 and showed that suppressor of Zeste 12 homolog protein levels were inversely correlated with the levels of miR-105 expression in clinical specimens...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28587163/a-tox21-approach-to-altered-epigenetic-landscapes-assessing-epigenetic-toxicity-pathways-leading-to-altered-gene-expression-and-oncogenic-transformation-in-vitro
#3
REVIEW
Craig L Parfett, Daniel Desaulniers
An emerging vision for toxicity testing in the 21st century foresees in vitro assays assuming the leading role in testing for chemical hazards, including testing for carcinogenicity. Toxicity will be determined by monitoring key steps in functionally validated molecular pathways, using tests designed to reveal chemically-induced perturbations that lead to adverse phenotypic endpoints in cultured human cells. Risk assessments would subsequently be derived from the causal in vitro endpoints and concentration vs...
June 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28557790/long-non-coding-rna-profile-in-mantle-cell-lymphoma-identifies-a-functional-lncrna-ror1-as1-associated-with-ezh2-prc2-complex
#4
Guangzhen Hu, Shiv K Gupta, Tammy P Troska, Asha Nair, Mamta Gupta
Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by rapid disease progression. The needs for new therapeutic strategies for MCL patients call for further understanding on the molecular mechanisms of pathogenesis of MCL. Recently, long noncoding RNAs (lncRNAs) have been recognized as key regulators of gene expression and disease development, however, the role of lncRNAs in non-Hodgkin lymphoma and specifically in MCL is still unknown. Next generation RNA-sequencing was carried out on MCL patient samples along with normal controls and data was analyzed...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28529604/dicer1-regulates-endometrial-carcinoma-invasion-via-histone-acetylation-and-methylation
#5
Bilan Li, Wen Lu, Junjie Qu, Yongli Zhang, Xiaoping Wan
Endometrial carcinoma (EC) is one of the most common gynecologic malignancy, but molecular mechanisms of the development and progression of EC remain unclear. Here we showed that the expression of DICER1 was negatively associated with the level of histone methylation, histone acetylation and PRC2 components SUZ12 and EZH2 in EC cells. In addition, knockdown of DICER1 significantly downregulated miR-200b and let-7i, which may then regulate their targets SUZ12 and EZH2. Furthermore, knockdown of DICER1 remarkably suppressed the expression of epithelial cell marker E-cadherin, induced the expression of mesenchymal cell marker Vimentin, and promoted the invasion of EC cells...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28508686/malignant-peripheral-nerve-sheath-tumor-of-the-femur-a-rare-diagnosis-supported-by-complete-immunohistochemical-loss-of-h3k27me3
#6
Masato Sugawara, Eisuke Kobayashi, Naofumi Asano, Akihiko Yoshida, Akira Kawai
The histological diagnosis of malignant peripheral nerve sheath tumor (MPNST) is challenging because of the wide morphological spectrum and suboptimal performance of conventional immunohistochemical markers. MPNST arising primarily in the bone is exceptional, and its definitive diagnosis, particularly out of the neurofibromatosis type 1 (NF1) context, is even more problematic. Recurrent inactivation of EED or SUZ12 in a majority of MPNSTs results in a complete loss of trimethylated histone H3 at lysine 27 (H3K27me3) immunoreactivity, making it a highly specific biomarker of MPNSTs...
May 1, 2017: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28446464/trf-mir-1280-suppresses-stem-cell-like-cells-and-metastasis-in-colorectal-cancer
#7
Bingqing Huang, Huipeng Yang, Xixi Cheng, Dan Wang, Shuyu Fu, Wencui Shen, Qi Zhang, Lijuan Zhang, Zhenyi Xue, Yan Li, Yurong Da, Qing Yang, Zesong Li, Li Liu, Liang Qiao, Ying Kong, Zhi Yao, Peng Zhao, Min Li, Rongxin Zhang
Several studies have shown that tRNAs can be enzymatically cleaved to generate distinct classes of tRNA-derived fragments (tRF). Here, we report that tRF/miR-1280, a 17-bp fragment derived from tRNA(Leu) and pre-miRNA, influences Notch signaling pathways that support the function of cancer stem-like cells (CSC) in colorectal cancer progression. tRF/miR-1280 expression was decreased in human specimens of colorectal cancer. Ectopic expression of tRF/miR-1280 reduced cell proliferation and colony formation, whereas its suppression reversed these effects...
April 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/28418861/brain-derived-neurotrophic-factor-involved-epigenetic-repression-of-ugt2b7-in-colorectal-carcinoma-a-mechanism-to-alter-morphine-glucuronidation-in-tumor
#8
Zi-Zhao Yang, Li Li, Ming-Cheng Xu, Hai-Xing Ju, Miao Hao, Jing-Kai Gu, Zai-Jie Jim Wang, Hui-Di Jiang, Lu-Shan Yu, Su Zeng
Uridine diphosphate-glucuronosyltransferase (UGT) 2B7, as one of significant drug enzymes, is responsible on the glucuronidation of abundant endobiotics or xenobiotics. We here report that it is markedly repressed in the tumor tissues of colorectal carcinoma (CRC) patients. Accordingly, morphine in CRC cells will stimulate the expression of its main metabolic enzyme, UGT2B7 during tolerance generation by activating the positive signals in histone 3, especially for trimethylated lysine 27 (H3K4Me3) and acetylated lysine 4 (H3K27Ac)...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412742/association-of-the-long-non-coding-rna-malat1-with-the-polycomb-repressive-complex-pathway-in-t-and-nk-cell-lymphoma
#9
Soo Hee Kim, Se Hoon Kim, Woo Ick Yang, Soo Jeong Kim, Sun Och Yoon
Recently, various long non-coding RNAs (lncRNAs) have been reported to have significant therapeutic or prognostic value. However, the expression of lncRNAs has not been investigated in T and NK cell lymphoma. Thus, we evaluated the biological and prognostic role of lncRNAs related to the polycomb repressive complex (PRC) and PRC markers in tissue samples and cell lines of T and NK cell lymphoma. Among the tested lncRNAs, MALAT1 was most highly expressed in clinical samples and cell lines. High expression of MALAT1 as well as BMI1 was related to poor prognosis in patients with mature T cell lymphoma...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28353387/recent-developments-in-surgical-pathology-of-the-uterine-corpus
#10
REVIEW
Krisztina Z Hanley, George G Birdsong, Marina B Mosunjac
There have been several updates recently on the classification of uterine tumors. Endometrial carcinomas have traditionally been divided into 2 types, but some are difficult to classify and do not fit readily into either of the currently recognized categories. The Cancer Genome Atlas Research Network has recently defined 4 new categories of endometrial cancer on the basis of mutational spectra, copy number alteration, and microsatellite instability, which might provide independent prognostic information beyond established risk factors...
April 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/28346433/a-cytosolic-ezh1-isoform-modulates-a-prc2-ezh1-epigenetic-adaptive-response-in-postmitotic-cells
#11
Beatrice Bodega, Federica Marasca, Valeria Ranzani, Alessandro Cherubini, Francesco Della Valle, Maria Victoria Neguembor, Michel Wassef, Alessio Zippo, Chiara Lanzuolo, Massimiliano Pagani, Valerio Orlando
The evolution of chromatin-based epigenetic cell memory may be driven not only by the necessity for cells to stably maintain transcription programs, but also by the need to recognize signals and allow plastic responses to environmental stimuli. The mechanistic role of the epigenome in adult postmitotic tissues, however, remains largely unknown. In vertebrates, two variants of the Polycomb repressive complex (PRC2-Ezh2 and PRC2-Ezh1) control gene silencing via methylation of histone H3 on Lys27 (H3K27me). Here we describe a reversible mechanism that involves a novel isoform of Ezh1 (Ezh1β)...
May 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28322158/effect-and-mechanism-of-curcumin-on-ezh2-mir-101-regulatory-feedback-loop-in-multiple-myeloma
#12
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
#13
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
#14
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 (WS) 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 WS by whole-exome sequencing and identified three mutations: a 25.4-kb deletion partially involving EZH2 and CUL1 (individual 1), a missense mutation (c...
June 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
#15
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
#16
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...
April 2017: EMBO Reports
https://www.readbyqxmd.com/read/28213670/emerging-genotype-phenotype-relationships-in-patients-with-large-nf1-deletions
#17
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
#18
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...
March 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28135235/an-allosteric-prc2-inhibitor-targeting-the-h3k27me3-binding-pocket-of-eed
#19
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
#20
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
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