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https://www.readbyqxmd.com/read/27902735/role-of-hepatic-specific-transcription-factors-and-polycomb-repressive-complex-2-during-induction-of-fibroblasts-to-hepatic-fate
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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)...
October 13, 2016: Der Pathologe
https://www.readbyqxmd.com/read/27659532/promoter-methylation-of-pcdh10-by-hotair-regulates-the-progression-of-gastrointestinal-stromal-tumors
#8
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...
September 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27634302/dynamic-protein-interactions-of-the-polycomb-repressive-complex-2-during-differentiation-of-pluripotent-cells
#9
Giorgio Oliviero, Gerard L Brien, Ariane Waston, Gundula Streubel, Emilia Jerman, Darrell Andrews, Benjamin Doyle, Nayla Munawar, Kieran Wynne, John Crean, Adrian P Bracken, Gerard Cagney
Polycomb proteins assemble to form complexes with important roles in epigenetic regulation. The Polycomb Repressive Complex 2 (PRC2) modulates the di- and tri-methylation of lysine 27 on histone H3, each of which are associated with gene repression. Although three subunits, EZH1/2, SUZ12, and EED, form the catalytic core of PRC2, a wider group of proteins associate with low stoichiometry. This raises the question of whether dynamic variation of the PRC2 interactome results in alternative forms of the complex during differentiation...
November 2016: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/27622053/th22-cells-control-colon-tumorigenesis-through-stat3-and-polycomb-repression-complex-2-signaling
#10
Danfeng Sun, Yanwei Lin, Jie Hong, Haoyan Chen, Nisha Nagarsheth, Dongjun Peng, Shuang Wei, Emina Huang, Jingyuan Fang, Ilona Kryczek, Weiping Zou
Th22 cells traffic to and retain in the colon cancer microenvironment, and target core stem cell genes and promote colon cancer stemness via STAT3 and H3K79me2 signaling pathway and contribute to colon carcinogenesis. However, whether Th22 cells affect colon cancer cell proliferation and apoptosis remains unknown. We studied the interaction between Th22 cells and colon cancer cells in the colon cancer microenvironment. Colon cancer proliferation was examined by flow cytometry analysis and H(3) thymidine incorporation...
August 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27582550/decreased-mir-320a-promotes-invasion-and-metastasis-of-tumor-budding-cells-in-tongue-squamous-cell-carcinoma
#11
Nan Xie, Cheng Wang, Zehang Zhuang, Jinson Hou, Xiqiang Liu, Yue Wu, Haichao Liu, Hongzhang Huang
We aimed to determine the specific miRNA profile of tumor budding cells and investigate the potential role of miR-320a in invasion and metastasis of tongue squamous cell carcinoma (TSCC). We collected tumor budding cells and paired central tumor samples from five TSCC specimens with laser capture microdissection and examined the specimens using a miRNA microarray. The specific miRNA signature of tumor budding cells was identified. We found that miR-320a was dramatically decreased in tumor budding cells. Knockdown of miR-320a significantly enhanced migration and invasion of TSCC cell lines...
August 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27550047/long-non-coding-rna-hotair-expression-in-diffuse-large-b-cell-lymphoma-in-relation-to-polycomb-repressive-complex-pathway-proteins-and-h3k27-trimethylation
#12
Eun Ji Oh, Soo Hee Kim, Woo Ick Yang, Young Hyeh Ko, Sun Och Yoon
BACKGROUND: A long non-coding RNA hox transcript antisense intergenic RNA (HOTAIR) is involved in epigenetic regulation through chromatin remodeling by recruiting polycomb repressive complex 2 (PRC2) proteins (EZH2, SUZ12, and EED) that induce histone H3 trimethylation at lysine 27 (H3K27me3). Deregulation of c-MYC and interaction between c-MYC and EZH2 are well known in lymphomagenesis; however, little is known about the expression status of HOTAIR in diffuse large B-cell lymphomas (DLBCLs)...
September 2016: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/27507049/the-pseudogene-derived-long-noncoding-rna-duxap8-promotes-gastric-cancer-cell-proliferation-and-migration-via-epigenetically-silencing-plekho1-expression
#13
Hong-Wei Ma, Min Xie, Ming Sun, Tian-Yu Chen, Rong-Rong Jin, Tian-Shi Ma, Qin-Nan Chen, Er-Bao Zhang, Xue-Zhi He, Wei De, Zhi-Hong Zhang
Gastric cancer (GC) is the third leading cause of cancer death due to its poor prognosis and limited treatment options. Evidence indicates that pseudogene-derived long noncoding RNAs (lncRNAs) may be important players in human cancer progression, including GC. In this paper, we report that a newly discovered pseudogene-derived lncRNA named DUXAP8, a 2107-bp RNA, was remarkably upregulated in GC. Additionally, a higher level of DUXAP8 expression in GC was significantly associated with greater tumor size, advanced clinical stage, and lymphatic metastasis...
August 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/27488116/proteomic-analysis-of-differentially-expressed-proteins-in-vitreous-humor-of-patients-with-retinoblastoma-using-itraq-coupled-esi-ms-ms-approach
#14
Jasmine Naru, Ritu Aggarwal, Usha Singh, Ashok Kumar Mohanty, Deepak Bansal, Navdeep Mangat, Nandita Kakkar, Navneet Agnihotri
There is close proximity of vitreous humor with the tumor bulk in eyes with retinoblastoma. This renders vitreous humor a promising source to evaluate disease-specific protein targets in retinoblastoma. We studied the differential proteome of vitreous fluid in retinoblastoma tumors (n = 4) as compared to controls (n = 4). The vitreous humor was depleted off the high abundant fraction using MARS-6 affinity column. Subsequently, the tryptic peptides were derivatised with iTRAQ labels. The labelled peptides were pooled and subjected to fractionation using bRPLC...
August 3, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27486969/crispr-cas9-guided-chromatin-immunoprecipitation-identifies-mir483-as-an-epigenetic-modulator-of-igf2-imprinting-in-tumors
#15
Yiqun Zhang, Ji-Fan Hu, Hong Wang, Jiuwei Cui, Sujun Gao, Andrew R Hoffman, Wei Li
The normally imprinted insulin-like growth factor II (IGF2) gene is aberrantly upregulated in a variety of human malignancies, yet the mechanisms underlying this dysregulation are still poorly defined. In this report, we used a novel CRISPR Cas9-guided chromatin immunoprecipitation assay to characterize the molecular components that participate in the control of IGF2 gene expression in human tumor cells. We found that miR483, an oncogenic intronic miRNA, binds to the most upstream imprinted IGF2 promoter, P2...
July 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27471434/high-ezh2-expression-is-correlated-to-metastatic-disease-in-pediatric-soft-tissue-sarcomas
#16
Maria Ramaglia, Velia D'Angelo, Adriana Iannotta, Daniela Di Pinto, Elvira Pota, Maria Carmen Affinita, Vittoria Donofrio, Maria Elena Errico, Angela Lombardi, Cristiana Indolfi, Fiorina Casale, Michele Caraglia
BACKGROUND: Enhancer of Zeste Drosophila Homologue 2 (EZH2) is a key regulator of transcription as a member of polycomb repressive complex 2 (PRC2) which exerts repression of downstream genes and is correlated to invasiveness and progression of different tumours. Therefore, we evaluated the expression of PRC2 proteins in pediatric soft tissue sarcoma (rhabdomyosarcoma, RMS and extraosseous Ewing sarcoma, EES) correlating them to the clinical outcome of the patients. METHODS: We analyzed PRC2 protein expression by quantitative real time PCR, western blotting and immunohistochemistry in 17 soft tissue sarcomas (11 RMS and 6 EES) enrolled at Paediatric Oncology Units of the Second University of Naples...
2016: Cancer Cell International
https://www.readbyqxmd.com/read/27461342/hypomethylation-coordinates-antagonistically-with-hypermethylation-in-cancer-development-a-case-study-of-leukemia
#17
Garima Kushwaha, Mikhail Dozmorov, Jonathan D Wren, Jing Qiu, Huidong Shi, Dong Xu
BACKGROUND: Methylation changes are frequent in cancers, but understanding how hyper- and hypomethylated region changes coordinate, associate with genomic features, and affect gene expression is needed to better understand their biological significance. The functional significance of hypermethylation is well studied, but that of hypomethylation remains limited. Here, with paired expression and methylation samples gathered from a patient/control cohort, we attempt to better characterize the gene expression and methylation changes that take place in cancer from B cell chronic lymphocyte leukemia (B-CLL) samples...
2016: Human Genomics
https://www.readbyqxmd.com/read/27450498/repressing-the-keratinocyte-genome-how-the-polycomb-complex-subunits-operate-in-concert-to-control-skin-and-hair-follicle-development
#18
Vladimir A Botchkarev, Andrei N Mardaryev
The Polycomb group proteins are transcriptional repressors that are critically important in the control of stem cell activity and maintenance of the identity of differentiated cells. Polycomb proteins interact with each other to form chromatin-associated repressive complexes (Polycomb repressive complexes 1 and 2) leading to chromatin compaction and gene silencing. However, the roles of the distinct components of the Polycomb repressive complex 2 in the control of skin development and keratinocyte differentiation remain obscure...
August 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27367027/inflammatory-related-gene-ikk%C3%AE-ikk%C3%AE-ikk%C3%AE-cooperates-to-determine-liver-cancer-stem-cells-progression-by-altering-telomere-via-heterochromatin-protein-1-hotair-axis
#19
Jiahui An, Mengying Wu, Xiaoru Xin, Zhuojia Lin, Xiaonan Li, Qidi Zheng, Xin Gui, Tianming Li, Hu Pu, Haiyan Li, Dongdong Lu
Cancer stem cells are associated with tumor recurrence. IKK is a protein kinase that is composed of IKKα, IKKβ, IKKγ. Herein, we demonstrate that IKKα plus IKKβ promoted and IKKγ inhibited liver cancer stem cell growth in vitro and in vivo. Mechanistically, IKKα plus IKKβ enhanced and IKKγ inhibited the interplay among HP1α, HP1β and HP1γ that competes for the interaction among HP1α, SUZ12, HEZ2. Therefore, IKKα plus IKKβ inhibited and IKKγ enhanced the activity of H3K27 methyltransferase SUZ12 and EZH2, which methylates H3K27 immediately sites on HOTAIR promoter region...
June 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27338022/rna-helicase-dead-box-protein-5-regulates-polycomb-repressive-complex-2-hox-transcript-antisense-intergenic-rna-function-in-hepatitis-b-virus-infection-and-hepatocarcinogenesis
#20
Hao Zhang, Zheng Xing, Saravana Kumar Kailasam Mani, Brigitte Bancel, David Durantel, Fabien Zoulim, Elizabeth J Tran, Philippe Merle, Ourania Andrisani
UNLABELLED: Chronic hepatitis B virus (HBV) infection is a major factor in hepatocellular carcinoma (HCC) pathogenesis by a mechanism not yet understood. Elucidating mechanisms of HBV-mediated hepatocarcinogenesis is needed to gain insights into classification and treatment of HCC. In HBV replicating cells, including virus-associated HCCs, suppressor of zeste 12 homolog (SUZ12), a core subunit of Polycomb repressive complex2 (PRC2), undergoes proteasomal degradation. This process requires the long noncoding RNA, Hox transcript antisense intergenic RNA (HOTAIR)...
October 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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