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https://www.readbyqxmd.com/read/28338656/focal-adhesion-kinase-depletion-reduces-human-hepatocellular-carcinoma-growth-by-repressing-enhancer-of-zeste-homolog-2
#1
Daniela Gnani, Ilaria Romito, Simona Artuso, Marco Chierici, Cristiano De Stefanis, Nadia Panera, Annalisa Crudele, Sara Ceccarelli, Elena Carcarino, Valentina D'Oria, Manuela Porru, Ezio Giorda, Karin Ferrari, Luca Miele, Erica Villa, Clara Balsano, Diego Pasini, Cesare Furlanello, Franco Locatelli, Valerio Nobili, Rossella Rota, Carlo Leonetti, Anna Alisi
Hepatocellular carcinoma (HCC) is the most common type of liver cancer in humans. The focal adhesion tyrosine kinase (FAK) is often over-expressed in human HCC and FAK inhibition may reduce HCC cell invasiveness. However, the anti-oncogenic effect of FAK knockdown in HCC cells remains to be clarified. We found that FAK depletion in HCC cells reduced in vitro and in vivo tumorigenicity, by inducing G2/M arrest and apoptosis, decreasing anchorage-independent growth, and modulating the expression of several cancer-related genes...
March 24, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28337379/long-intergenic-non-coding-rna-00152-promotes-renal-cell-carcinoma-progression-by-epigenetically-suppressing-p16-and-negatively-regulates-mir-205
#2
Yongjun Wang, Jianzhen Liu, Hongzhong Bai, Yi Dang, Pei Lv, Shucai Wu
Long non-coding RNAs (lncRNAs) have been reported to play important roles in the tumorigenesis and development of several human cancers. Long intergenic non-coding RNA 152 (LINC00152) is significantly up-regulated in some solid tumors. However, the role of LINC00152 in the pathogenesis and development of renal cell carcinoma (RCC) remains largely unclear. In the study, we showed that LINC00152 expression was up-regulated in RCC tissues compared with adjacent normal tissues and revealed that LINC00152 expression was positively correlated with lymph node metastasis, higher TNM stage, and poor over survival (OS) time in RCC patients...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28335073/clinical-characteristics-and-whole-exome-transcriptome-sequencing-of-coexisting-chronic-myeloid-leukemia-and-myelofibrosis
#3
Malathi Kandarpa, Yi-Mi Wu, Dan Robinson, Patrick William Burke, Arul M Chinnaiyan, Moshe Talpaz
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell (HSC) disorders that can be classified on the basis of genetic, clinical, phenotypic features. Genetic lesions such as JAK2 mutations and BCR-ABL translocation are often mutually exclusive in MPN patients and lead to essential thrombocythemia, polycythemia vera or myelofibrosis (ET/PV/MF) or chronic myeloid leukemia, respectively. Nevertheless, coexistence of these genetic aberrations in the same patient has been reported. Whether these aberrations occur in the same stem cell or a different cell is unclear, but an unstable genome in the HSCs seems to be the common antecedent...
March 23, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28332284/ezh2-mediated-repression-of-dkk1-promotes-hepatic-stellate-cell-activation-and-hepatic-fibrosis
#4
Yang Yang, Xiao-Xia Chen, Wan-Xia Li, Xiao-Qin Wu, Cheng Huang, Juan Xie, Yu-Xin Zhao, Xiao-Ming Meng, Jun Li
EZH2, a histone H3 lysine-27-specific methyltransferase, is involved in diverse physiological and pathological processes including cell proliferation and differentiation. However, the role of EZH2 in liver fibrosis is largely unknown. In this study, it was identified that EZH2 promoted Wnt pathway-stimulated fibroblasts in vitro and in vivo by repressing Dkk-1, which is a Wnt pathway antagonist. The expression of EZH2 was increased in CCl4 -induced rat liver and primary HSCs as well as TGF-β1-treated HSC-T6, whereas the expression of Dkk1 was reduced...
March 23, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28329683/inactivation-of-ezh2-upregulates-gfi1-and-drives-aggressive-myc-driven-group-3-medulloblastoma
#5
BaoHan T Vo, Chunliang Li, Marc A Morgan, Ilan Theurillat, David Finkelstein, Shaela Wright, Judith Hyle, Stephanie M C Smith, Yiping Fan, Yong-Dong Wang, Gang Wu, Brent A Orr, Paul A Northcott, Ali Shilatifard, Charles J Sherr, Martine F Roussel
The most aggressive of four medulloblastoma (MB) subgroups are cMyc-driven group 3 (G3) tumors, some of which overexpress EZH2, the histone H3K27 mono-, di-, and trimethylase of polycomb-repressive complex 2. Ezh2 has a context-dependent role in different cancers as an oncogene or tumor suppressor and retards tumor progression in a mouse model of G3 MB. Engineered deletions of Ezh2 in G3 MBs by gene editing nucleases accelerated tumorigenesis, whereas Ezh2 re-expression reversed attendant histone modifications and slowed tumor progression...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28329675/trimethylation-and-acetylation-of-%C3%AE-catenin-at-lysine-49-represent-key-elements-in-esc-pluripotency
#6
Katrin Hoffmeyer, Dirk Junghans, Benoit Kanzler, Rolf Kemler
Wnt/β-catenin signaling is required for embryonic stem cell (ESC) pluripotency by inducing mesodermal differentiation and inhibiting neuronal differentiation; however, how β-catenin counter-regulates these differentiation pathways is unknown. Here, we show that lysine 49 (K49) of β-catenin is trimethylated (β-catMe3) by Ezh2 or acetylated (β-catAc) by Cbp. Significantly, β-catMe3 acts as a transcriptional co-repressor of the neuronal differentiation genes sox1 and sox3, whereas β-catAc acts as a transcriptional co-activator of the key mesodermal differentiation gene t-brachyury (t-bra)...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28328977/jmjd3-aids-in-reprogramming-of-bone-marrow-progenitor-cells-to-hepatic-phenotype-through-epigenetic-activation-of-hepatic-transcription-factors
#7
Veena Kochat, Zaffar Equbal, Prakash Baligar, Vikash Kumar, Madhulika Srivastava, Asok Mukhopadhyay
The strictly regulated unidirectional differentiation program in some somatic stem/progenitor cells has been found to be modified in the ectopic site (tissue) undergoing regeneration. In these cases, the lineage barrier is crossed by either heterotypic cell fusion or direct differentiation. Though studies have shown the role of coordinated genetic and epigenetic mechanisms in cellular development and differentiation, how the lineage fate of adult bone marrow progenitor cells (BMPCs) is reprogrammed during liver regeneration and whether this lineage switch is stably maintained are not clearly understood...
2017: PloS One
https://www.readbyqxmd.com/read/28327608/kdm4b-histone-demethylase-and-g9a-regulate-expression-of-vascular-adhesion-proteins-in-cerebral-microvessels
#8
Ji-Young Choi, Sang-Sun Yoon, Sang-Eun Kim, Sangmee Ahn Jo
Intercellular adhesion molecule 1 (ICAM1) mediates the adhesion and transmigration of leukocytes across the endothelium, promoting inflammation. We investigated the epigenetic mechanism regulating ICAM1 expression. The pro-inflammatory cytokine TNF-α dramatically increased ICAM1 mRNA and protein levels in human brain microvascular endothelial cells and mouse brain microvessels. Chromatin immunoprecipitation revealed that TNF-α reduced methylation of histone H3 at lysines 9 and 27 (H3K9 and H3K27), well-known residues involved in gene suppression...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28323035/naturally-occurring-anti-cancer-agents-targeting-ezh2
#9
Fahimeh Shahabipour, Michele Caraglia, Muhammed Majeed, Giuseppe Derosa, Pamela Maffioli, Amirhossein Sahebkar
Natural products are considered as promising tools for the prevention and treatment of cancer. The enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase unit of polycomb repressor complexes such as PRC2 complex that has oncogenic roles through interference with growth and metastatic potential. Several agents targeting EZH2 has been discovered but they often induce side effects in clinical trials. Recently, EZH2 has emerged as a potential target of natural products with documented anti-cancer effects and this discloses a new scenario for the development of EZH2 inhibitory strategies with agents with low cytotoxic detrimental effects...
March 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28322158/effect-and-mechanism-of-curcumin-on-ezh2-mir-101-regulatory-feedback-loop-in-multiple-myeloma
#10
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/28320776/epigenomic-promoter-alterations-amplify-gene-isoform-and-immunogenic-diversity-in-gastric-adenocarcinoma
#11
Aditi Qamra, Manjie Xing, Nisha Padmanabhan, Jeffrey Jun Ting Kwok, Shenli Zhang, Xu Chang, Yan Shan Leong, Ai Ping Lee Lim, Qianqao Tang, WenFong Ooi, Joyce Suling Lin, Tannistha Nandi, Xiaosai Yao, Xuewen Ong, Minghui Lee, Su Ting Tay, Angie Tan Lay Keng, Erna Gondo Santoso, Cedric Chuan Young Ng, Alvin Ng, Apinya Jusakul, Duane Smoot, Hassan Ashktorab, Sun Young Rha, Khay Guan Yeoh, Wei Peng Yong, Pierce K H Chow, Weng Hoong Chan, Hock Soo Ong, Khee Chee Soo, Kyoung-Mee Kim, Wai Keong Wong, Steven G Rozen, Bin Tean Teh, Dennis Kappei, Jeeyun Lee, John Connolly, Patrick Tan
Promoter elements play important roles in isoform and cell-type specific expression. We surveyed the epigenomic promoter landscape of gastric adenocarcinoma (GC), analyzing 110 chromatin profiles (H3K4me3, H3K4me1, H3K27ac) of primary GCs, GC lines, and non-malignant gastric tissues. We identified ~2000 promoter alterations (somatic promoters), many deregulated in various epithelial malignancies and mapping frequently to alternative promoters within the same gene, generating potential pro-oncogenic isoforms (RASA3)...
March 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28320739/a-covalently-bound-inhibitor-triggers-ezh2-degradation-through-chip-mediated-ubiquitination
#12
Xu Wang, Wei Cao, Jianjun Zhang, Ming Yan, Qin Xu, Xiangbing Wu, Lixin Wan, Zhiyuan Zhang, Chenping Zhang, Xing Qin, Meng Xiao, Dongxia Ye, Yuyang Liu, Zeguang Han, Shaomeng Wang, Li Mao, Wenyi Wei, Wantao Chen
Enhancer of zeste homolog 2 (EZH2) has been characterized as a critical oncogene and a promising drug target in human malignant tumors. The current EZH2 inhibitors strongly suppress the enhanced enzymatic function of mutant EZH2 in some lymphomas. However, the recent identification of a PRC2- and methyltransferase-independent role of EZH2 indicates that a complete suppression of all oncogenic functions of EZH2 is needed. Here, we report a unique EZH2-targeting strategy by identifying a gambogenic acid (GNA) derivative as a novel agent that specifically and covalently bound to Cys668 within the EZH2-SET domain, triggering EZH2 degradation through COOH terminus of Hsp70-interacting protein (CHIP)-mediated ubiquitination...
March 20, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28315733/wt1-ameliorates-podocyte-injury-via-repression-of-ezh2-%C3%AE-catenin-pathway-in-diabetic-nephropathy
#13
Jiao Wan, Xiaoyan Hou, Zhanmei Zhou, Jian Geng, Jianwei Tian, Jing Nie, Xiaoyan Bai
Epigenetic modulation of podocyte injury plays a pivotal role in diabetic nephropathy (DN). Wilm's tumor 1 (WT1) has been found to have opposing roles with β-catenin in podocyte biology. Herein, we asked whether the histone methyltransferase enzyme enhancer of zeste homolog 2 (EZH2) promotes WT1-induced podocyte injury via β-catenin activation and the underlying mechanisms. We found that WT1 antagonized EZH2 and ameliorated β-catenin-mediated podocyte injury as demonstrated by attenuated podocyte mesenchymal transition, maintenance of podocyte architectural integrity, decreased podocyte apoptosis and oxidative stress...
March 15, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28314309/elevated-metabolic-activity-on-18-f-fdg-pet-ct-is-associated-with-the-expression-of-ezh2-in-non-small-cell-lung-cancer
#14
Gouji Toyokawa, Kazuki Takada, Tatsuro Okamoto, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Takaki Akamine, Shinkichi Takamori, Masakazu Katsura, Fumihiro Shoji, Ryuji Hamamoto, Yoshinao Oda, Yoshihiko Maehara
BACKGROUND/AIM: Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that is deeply involved in the pathogenesis of lung cancer. We evaluated the metabolic characteristics of non-small cell lung cancer (NSCLC) in patients with and without expression of EZH2 using (18)F-fluorodeoxyglucose positron-emission tomography/ computed tomography ((18)F-FDG PET/CT). MATERIALS AND METHODS: The EZH2 protein expression of 268 patients with resected NSCLC, whose preoperative (18)F-FDG PET/CT information was available, was evaluated by immunohistochemistry with clone 6A10 antibody; cases with Allred score ≥3 were considered positive...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28304223/metastatic-clival-chordoma-a-case-report-of-multiple-extraneural-metastases-following-resection-and-proton-beam-radiotherapy-in-a-5-year-old-boy
#15
Martin J Rutkowski, Harjus S Birk, Matthew D Wood, Arie Perry, Theodore Nicolaides, Christopher P Ames, Nalin Gupta
The authors report the case of a 5-year-old boy in whom extraneural metastases developed 5 years after he underwent an occipitocervical fusion and transoral approach to treat a clival chordoma without local recurrence. Following primary resection, the patient's postoperative course was complicated by recurrent meningitis secondary to CSF leak, which responded to antibiotics, and communicating hydrocephalus, for which a ventriculoperitoneal shunt was placed. The patient then underwent postoperative proton beam radiotherapy...
March 17, 2017: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/28302719/a-repressive-role-of-enhancer-of-zeste-homolog-2-in-11%C3%AE-hydroxysteroid-dehydrogenase-type-2-expression-in-human-placenta
#16
Rujuan Zuo, Xiaohui Liu, Wangsheng Wang, Wenjiao Li, Hao Ying, Kang Sun
The expression of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which acts as a placental glucocorticoid barrier, is silenced in the cytotrophoblasts but substantially up-regulated during syncytialization. However, the repressive mechanism of 11β-HSD2 expression before syncytialization and how this repression is lifted during syncytialization remain mostly unresolved. Here we found that enhancer of zeste homolog 2 (EZH2) accounts for the silence of 11β-HSD2 expression via trimethylation of histone H3 lysine 27 (H3K27me3) at the promoter of 11β-HSD2 gene...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28296507/lncrna-pvt1-epigenetically-silences-mir-195-and-modulates-emt-and-chemoresistance-in-cervical-cancer-cells
#17
Ching-Ju Shen, Ya-Min Cheng, Chiu-Lin Wang
The plasmacytoma variant translocation 1 gene (PVT1) is an oncogenic lncRNA with regulative effect on chemosensitivity in cervical cancer. However, the underlying mechanisms were not fully understood. In this study, HPV16 positive CaSki and SiHa cells were used as in-vitro cell model. Knockdown of HPV16 E7 significantly inhibited PVT1 and restored miR-195 expression. PVT1 directly interacts with EZH2 and the complex anchors in the promoter region of miR-195. PVT1 overexpression resulted in increased H3K27me3 levels in the miR-195 promoter region, while PVT1 knockdown decreased H3K27me3 levels in the promoter region...
March 15, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28292935/selective-killing-of-smarca2-and-smarca4-deficient-small-cell-carcinoma-of-the-ovary-hypercalcemic-type-cells-by-inhibition-of-ezh2-in-vitro-and-in-vivo-preclinical-models
#18
Elayne Chan-Penebre, Kelli Armstrong, Allison Drew, Alexandra R Grassian, Igor Feldman, Sarah K Knutson, Kristy Kuplast-Barr, Maria Roche, John Campbell, Peter Ho, Robert A Copeland, Richard Chesworth, Jesse J Smith, Heike Keilhack, Scott A Ribich
The SWI/SNF complex is a major regulator of gene expression and is increasingly thought to play an important role in human cancer, as evidenced by the high frequency of subunit mutations across virtually all cancer types. We previously reported that in preclinical models, malignant rhabdoid tumors, which are deficient in the SWI/SNF core component INI1 (SMARCB1), are selectively killed by inhibitors of the H3K27 histone methyltransferase EZH2. Given the demonstrated antagonistic activities of the SWI/SNF complex and the EZH2-containing PRC2 complex, we investigated whether additional cancers with SWI/SNF mutations are sensitive to selective EZH2 inhibition...
March 14, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28292020/long-non-coding-rna-hnf1a-as1-promotes-hepatocellular-carcinoma-cell-proliferation-by-repressing-nkd1-and-p21-expression
#19
Cong Wang, Lin Mou, Hai-Xia Chai, Feng Wang, Yun-Zhi Yin, Xiao-Yu Zhang
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Recent evidences have demonstrated that long non-coding RNAs (lncRNAs) act as key regulators of tumor development and progression including HCC. In the study, we showed that the expression level of HNF1A-AS1 was up-regulated in HCC cell lines. Furthermore, CCK-8 cell proliferation assays and cell cycle analysis showed that HNF1A-AS1 over-expression facilitated HCC cell proliferation by promoting the cell proliferation and S-phase progression, whereas HNF1A-AS1 knockdown had the opposite effect...
March 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28286564/targeting-histone-methylation-for-colorectal-cancer
#20
REVIEW
Tao Huang, Chengyuan Lin, Linda L D Zhong, Ling Zhao, Ge Zhang, Aiping Lu, Jiang Wu, Zhaoxiang Bian
As a leading cause of cancer deaths worldwide, colorectal cancer (CRC) results from accumulation of both genetic and epigenetic alterations. Disruption of epigenetic regulation in CRC, particularly aberrant histone methylation mediated by histone methyltransferases (HMTs) and demethylases (HDMs), have drawn increasing interest in recent years. In this paper, we aim to review the roles of histone methylation and associated enzymes in the pathogenesis of CRC, and the development of small-molecule modulators to regulate histone methylation for treating CRC...
January 2017: Therapeutic Advances in Gastroenterology
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