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https://www.readbyqxmd.com/read/28634230/similarity-in-gene-regulatory-networks-suggests-that-cancer-cells-share-characteristics-of-embryonic-neural-cells
#1
Zan Zhang, Anhua Lei, Liyang Xu, Lu Chen, Yonglong Chen, Xuena Zhang, Yan Gao, Xiaoli Yang, Min Zhang, Ying Cao
Cancer cells are immature cells resulting from cellular reprogramming by gene misregulation, and re-differentiation is expected to reduce malignancy. It is unclear, however, whether cancer cells can undergo terminal differentiation. Here, we show that, inhibition of the epigenetic modification enzymes enhancer of zeste homolog 2 (EZH2), histone deacetylases (HDACs) 1 and 3, lysine demethylase 1A (LSD1), or DNA methyltransferase 1 (DNMT1), which all promote cancer development and progression, leads to postmitotic neuron-like differentiation with loss of malignant features in distinct solid cancer cell lines...
June 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28626218/molecular-characterization-of-ezh2-mutant-patients-with-myelodysplastic-myeloproliferative-neoplasms
#2
J Rinke, J P Müller, M F Blaess, A Chase, M Meggendorfer, V Schäfer, N Winkelmann, C Haferlach, N C P Cross, A Hochhaus, T Ernst
Mutations in the epigenetic regulator gene EZH2 are frequently observed in patients with myelodysplastic/myeloproliferative neoplasms (MDS/MPN; 10-13%) and are associated with a poor outcome. To gain more insight into EZH2 pathology we sought to genetically characterize a cohort of 41 EZH2-mutated MDS/MPN patients using targeted deep next generation sequencing (NGS), colony forming progenitor assays and transcriptome analysis. Stable shRNA-mediated downregulation of EZH2 was performed in MDS derived F-36P, MOLM-13 and OCI-M2 cells to study EZH2 specific changes...
June 19, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28624787/long-non-coding-rna-uca1-promotes-gallbladder-cancer-progression-by-epigenetically-repressing-p21-and-e-cadherin-expression
#3
Qiang Cai, Longyang Jin, Shouhua Wang, Di Zhou, Jiandong Wang, Zhaohui Tang, Zhiwei Quan
A growing number of studies indicated that long non-coding RNAs (lncRNAs) determine some cellular processes in cancer, such as proliferation, metastasis and differentiation. Urothelial carcinoma associated 1 (UCA1), an lncRNA, had been reported for its overexpression and oncogenic effect on various human cancers. In this study, we found that UCA1 was significantly overexpressed in gallbladder cancer (GBC) and positively correlated with tumor size, lymph node metastasis, TNM stage and short survival time. Moreover, UCA1 promoted GBC cell proliferation and metastasis in vitro and tumor growth in vivo...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28623912/role-of-epigenetics-microrna-axis-in-drug-resistance-of-multiple-myeloma
#4
REVIEW
Nasrin Rastgoo, Jahangir Abdi, Jian Hou, Hong Chang
Despite administration of novel therapies, multiple myeloma (MM) remains incurable with resistance to drugs leading to relapse in most patients. Thus, it is critical to understand the detailed mechanisms underlying the drug resistance of MM and develop more effective therapeutic strategies. Genetic abnormalities are well known to play a central role in MM pathogenesis and therapy resistance; however, epigenetic aberrations mainly affecting the patterns of DNA methylation/histone modifications of genes (especially tumor suppressors) and miRNAs have also been shown to be involved...
June 17, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28622624/primary-myelofibrosis-older-age-and-high-jak2v617f-allele-burden-are-associated-with-elevated-plasma-high-sensitivity-c-reactive-protein-levels-and-a-phenotype-of-progressive-disease
#5
Giovanni Barosi, Margherita Massa, Rita Campanelli, Gabriela Fois, Paolo Catarsi, Gianluca Viarengo, Laura Villani, Valentina Poletto, Tiziana Bosoni, Umberto Magrini, Robert P Gale, Vittorio Rosti
We measured plasma levels of high-sensitivity C-reactive protein (hs-CRP) in 526 subjects with primary myelofibrosis (PMF). Thirty-eight percent had an elevated hs-CRP level (≥0.3mg/dL). Elevated hs-CRP levels were associated with a progressive disease phenotype, including anemia, high white blood cell count, low platelet count, increased splenomegaly, increased risk of blast transformation, and worse survival. Age≥52years, but no other demographic characteristics, was associated with an elevated hs-CRP level in multivariable logistic regression (odds ratio [OR], 4...
June 7, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28620234/ezh2-mediated-epigenetic-silencing-of-timp2-promotes-ovarian-cancer-migration-and-invasion
#6
Xiaoqing Yi, Jianfeng Guo, Jing Guo, Si Sun, Ping Yang, Junjie Wang, Yuan Li, Lisha Xie, Jing Cai, Zehua Wang
Enhancer of zeste homolog 2 (EZH2) is often increased in malignant tumors and is involved in metastasis. EZH2 silences gene expression by tri-methylating the lysine 27 residue of histone H3 (H3K27me3). However, the mechanism underlying EZH2 promotion of ovarian cancer metastasis remains elusive. Here, we showed that EZH2 is up-regulated in ovarian cancer and is associated with tumor metastasis and poor survival by mRNA sequencing and microarray results from databases. Tissue microarray and immunohistochemistry results revealed that EZH2 was negatively correlated with the expression of tissue inhibitor of metalloproteinases 2 (TIMP2)...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28620206/analysis-of-m%C3%A3-ller-glia-specific-genes-and-their-histone-modification-using-hes1-promoter-driven-egfp-expressing-mouse
#7
Kazuko Ueno, Toshiro Iwagawa, Genki Ochiai, Hideto Koso, Hiromitsu Nakauchi, Masao Nagasaki, Yutaka Suzuki, Sumiko Watanabe
Retinal neurons and Müller glia are generated from a common population of multipotent retinal progenitor cells. We purposed to identify Müller glia-specific molecular signatures during retinal development. Using transgenic mice carrying the Hes1 promoter (pHes1) followed by EGFP, we purified EGFP-positive Müller glia and other EGFP-negative retinal cells from developing retinas and subjected them to RNA sequencing analysis. Gene expression pattern of EGFP-positive cell was similar to genes expressed in retinal progenitors, and they were downregulated in other cell lineages...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615992/overexpression-of-lncrna-hoxa11-as-promotes-cell-epithelial-mesenchymal-transition-by-repressing-mir-200b-in-non-small-cell-lung-cancer
#8
Jian-Hui Chen, Li-Yang Zhou, Suo Xu, Yu-Long Zheng, Yu-Feng Wan, Cheng-Ping Hu
BACKGROUND: Recent studies have verified that long noncoding RNAs (lncRNAs) involved in many biological functions and play crucial roles in human cancers progression, the study aimed to detect the association between long non-coding RNA HOXA11-AS and epithelial-mesenchymal transition (EMT) process in non-small cell lung cancer (NSCLC). METHODS: The lncRNA HOXA11-AS expression levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR) assays in 78 paired of tumor tissue and adjacent normal tissue samples in NSCLC patients...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28612962/amygdalar-expression-of-the-microrna-mir-101a-and-its-target-ezh2-contribute-to-rodent-anxiety-like-behavior
#9
Joshua L Cohen, Nateka L Jackson, Mary E Ballestas, William M Webb, Farah D Lubin, Sarah M Clinton
A greater understanding of neural mechanisms contributing to anxiety is needed in order to develop better therapeutic interventions. The current study interrogates a novel molecular mechanism that shapes anxiety-like behavior, demonstrating that the microRNA miR-101a-3p and its target, enhancer of zeste homolog 2 (Ezh2) in the amygdala, contribute to rodent anxiety-like behavior. We utilized rats that were selectively-bred for differences in emotionality and stress reactivity, showing that high novelty responding (HR) rats, which display low trait anxiety, have lower miR-101a-3p levels in the amygdala compared to low novelty responding (LR) rats that characteristically display high trait anxiety...
June 14, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28612725/-the-biological-complexity-of-polycomb-group-proteins-the-case-of-ezh2
#10
Myriam Koubi, Christian Chabannon, Estelle Duprez
Polycomb Group proteins (PcG) are repressive epigenetic factors essential for development and involved in numerous cancer processes, yet their modes of action and recruitment to specific genomic loci are not fully understood. Recently, it has been shown that the PcG protein recruitment is a dynamic process, contrary to what was foreseen in the initial hierarchical model. In addition, EZH2, a key PcG protein, can be associated to transcribed genes, challenging the former function of PcG proteins as transcriptional repressors...
May 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28612220/individual-outcome-prediction-for-myelodysplastic-syndrome-mds-and-secondary-acute-myeloid-leukemia-from-mds-after-allogeneic-hematopoietic-cell-transplantation
#11
Michael Heuser, Razif Gabdoulline, Patrick Löffeld, Vera Dobbernack, Henriette Kreimeyer, Mira Pankratz, Madita Flintrop, Alessandro Liebich, Sabrina Klesse, Victoria Panagiota, Michael Stadler, Martin Wichmann, Rabia Shahswar, Uwe Platzbecker, Christian Thiede, Thomas Schroeder, Guido Kobbe, Robert Geffers, Brigitte Schlegelberger, Gudrun Göhring, Hans-Heinrich Kreipe, Ulrich Germing, Arnold Ganser, Nicolaus Kröger, Christian Koenecke, Felicitas Thol
We integrated molecular data with available prognostic factors in patients undergoing allogeneic hematopoietic cell transplantation (alloHCT) for myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia (sAML) from MDS to evaluate their impact on prognosis. Three hundred four patients were sequenced for mutations in 54 genes. We used a Cox multivariate model and competing risk analysis with internal and cross validation to identify factors prognostic of overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM)...
June 13, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28604389/a-cullin-4b-ring-e3-ligase-complex-fine-tunes-pancreatic-%C3%AE-cell-paracrine-interactions
#12
Qing Li, Min Cui, Fan Yang, Na Li, Baichun Jiang, Zhen Yu, Daolai Zhang, Yijing Wang, Xibin Zhu, Huili Hu, Pei-Shan Li, Shang-Lei Ning, Si Wang, Haibo Qi, Hechen Song, Dongfang He, Amy Lin, Jingjing Zhang, Feng Liu, Jiajun Zhao, Ling Gao, Fan Yi, Tian Xue, Jin-Peng Sun, Yaoqin Gong, Xiao Yu
Somatostatin secreted by pancreatic δ cells mediates important paracrine interactions in Langerhans islets, including maintenance of glucose metabolism through the control of reciprocal insulin and glucagon secretion. Disruption of this circuit contributes to the development of diabetes. However, the precise mechanisms that control somatostatin secretion from islets remain elusive. Here, we found that a super-complex comprising the cullin 4B-RING E3 ligase (CRL4B) and polycomb repressive complex 2 (PRC2) epigenetically regulates somatostatin secretion in islets...
June 12, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28602614/mir-203-interplays-with-polycomb-repressive-complexes-to-regulate-the-proliferation-of-neural-stem-progenitor-cells
#13
Pei-Pei Liu, Gang-Bin Tang, Ya-Jie Xu, Yu-Qiang Zeng, Shuang-Feng Zhang, Hong-Zhen Du, Zhao-Qian Teng, Chang-Mei Liu
The polycomb repressive complexes 1 (PRC1) and 2 (PRC2) are two distinct polycomb group (PcG) proteins that maintain the stable silencing of specific sets of genes through chromatin modifications. Although the PRC2 component EZH2 has been known as an epigenetic regulator in promoting the proliferation of neural stem/progenitor cells (NSPCs), the regulatory network that controls this process remains largely unknown. Here we show that miR-203 is repressed by EZH2 in both embryonic and adult NSPCs. MiR-203 negatively regulates the proliferation of NSPCs...
June 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28599500/notable-roles-of-ezh2-and-dnmt1-in-epigenetic-dormancy-of-the-shp1-gene-during-the-progression-of-chronic-myeloid-leukaemia
#14
Jing Wang, Luoming Hua, Ming Guo, Lin Yang, Xiaojun Liu, Yanmeng Li, Xiaoyan Shang, Jianmin Luo
Tumor development is associated with the methylation of cytosine-guanine (CpG) islands. The occurrence of methylation requires several factors, such as DNA methylation systems and polycomb group (PcG) proteins. At present, novel drugs are needed for the treatment of chronic myeloid leukaemia (CML), particularly considering the current prognosis of CML. The methylation status of the Src homology 2 domain-containing tyrosine phosphatase 1 (SHP1) gene, a negative regulator of signal transduction, has been identified as being altered in numerous haematological malignancies...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28588641/the-significant-pathways-and-genes-underlying-the-colon-cancer-treatment-by-the-traditional-chinese-medicine-phy906
#15
Ziyuan Su, Changyu Zhou, Shaoyou Qin, Erna Jia, Zhenting Wu
BACKGROUND: We attempted to explore the molecular mechanism underlying PHY906 intervention of colon cancer. METHODS: The microarray data of tumors treated by PHY906 and PBS alone were downloaded from the public Gene Expression Omnibus database. The dataset was further analyzed for the differentially expressed genes (DEGs) and their related biological functions were analyzed, followed by function and pathways. Protein-protein interaction (PPI) network was constructed and the significant nodes were screened by network centralities and then the significant modules analysis...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28587390/microrna-137-acts-as-a-tumor-suppressor-in-osteosarcoma-by-targeting-enhancer-of-zeste-homolog-2
#16
Qiong Feng, Qing Wu, Xing Liu, Yanfei Xiong, Hui Li
MicroRNA (miR) are short non-coding RNA that bind to the 3'-untranslational region of their target genes, inhibiting translation and causing mRNA degradation. miR deregulation has been implicated in human cancer; however, the detailed regulatory mechanism of miR-137 in osteosarcoma (OS) remains largely unknown. In the present study, miR-137 and enhancer of zeste homologue 2 (EZH2) mRNA and protein expression levels were analyzed using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively...
June 2017: Experimental and Therapeutic 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
#17
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/28582660/the-phytochemical-3-3-diindolylmethane-decreases-expression-of-ar-controlled-dna-damage-repair-genes-through-repressive-chromatin-modifications-and-is-associated-with-dna-damage-in-prostate-cancer-cells
#18
Zoraya Palomera-Sanchez, Gregory W Watson, Carmen P Wong, Laura M Beaver, David E Williams, Roderick H Dashwood, Emily Ho
Androgen receptor (AR) is a transcription factor involved in normal prostate physiology and prostate cancer (PCa) development. 3,3'-Diindolylmethane (DIM) is a promising phytochemical agent against PCa that affects AR activity and epigenetic regulators in PCa cells. However, whether DIM suppresses PCa via epigenetic regulation of AR target genes is unknown. We assessed epigenetic regulation of AR target genes in LNCaP PCa cells and showed that DIM treatment led to epigenetic suppression of AR target genes involved in DNA repair (PARP1, MRE11, DNA-PK)...
May 25, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28581456/epigenetic-silencing-of-irf1-dysregulates-type-iii-interferon-responses-to-respiratory-virus-infection-in-epithelial-to-mesenchymal-transition
#19
Jun Yang, Bing Tian, Hong Sun, Roberto P Garofalo, Allan R Brasier
Chronic oxidative injury produced by airway disease triggers a transforming growth factor-β (TGF-β)-mediated epigenetic reprogramming known as the epithelial-mesenchymal transition (EMT). We observe that EMT silences protective mucosal interferon (IFN)-I and III production associated with enhanced rhinovirus (RV) and respiratory syncytial virus (RSV) replication. Mesenchymal transitioned cells are defective in inducible interferon regulatory factor 1 (IRF1) expression by occluding RelA and IRF3 access to the promoter...
June 5, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28580773/hbx-mediated-decrease-of-aim2-contributes-to-hepatocellular-carcinoma-metastasis
#20
Shi-Lu Chen, Li-Li Liu, Shi-Xun Lu, Rong-Zhen Luo, Chun-Hua Wang, Hong Wang, Shao-Hang Cai, Xia Yang, Dan Xie, Chris Zhiyi Zhang, Jing-Ping Yun
Tumor metastasis is responsible for the high mortality rates in patients with hepatocellular carcinoma (HCC). Absent in Melanoma 2 (AIM2) has been implicated in inflammation and carcinogenesis, but its role in HCC metastasis remains unknown. Here, we show that AIM2 protein expression was noticeably reduced in HCC cell lines and clinical samples. A reduction in AIM2 was closely associated with higher serum AFP levels, vascular invasion, poor tumor differentiation, an incomplete tumor capsule and unfavorable postsurgical survival odds...
June 5, 2017: Molecular Oncology
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