DOCSLIB.ORG

Analysis of Genetic Susceptibility to Type Ii Diabetes in Mice

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Analysis of Genetic Susceptibility to Type Ii Diabetes in Mice ANALYSIS OF GENETIC SUSCEPTIBILITY TO TYPE II DIABETES IN MICE By SOHA N. YAZBEK Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy Dissertation advisor: Dr. Joseph H. Nadeau Department of Genetics CASE WESTERN RESERVE UNIVERSITY August 2010 CASE WESTERN RESREVER UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of Soha N. Yazbek ________________________________________________________ candidate for the PhD degree* Mark Adams (signed)__________________________________________________ (chair of the committee) Joseph Nadeau __________________________________________________ Colleen Croniger ____________________________________________________ Mitchell Drumm ____________________________________________________ May 4, 2010 (date) _______________________ *We also certify that written approval has been obtained for any proprietary material contained therein. 2 Dedication I dedicate this work to the soul of my late grandmother, Mountaha Harb, who died two years short of seeing what I have become. I am sure she is watching over me and I hope she is proud. 3 Table of Contents Dedication ............................................................................................................................................. 3 TABLE OF CONTENTS.......................................................................................................... 4 List of tables ......................................................................................................................................... 7 List of figures ........................................................................................................................................ 8 Acknowledgement ............................................................................................................................... 9 Abstract ................................................................................................................................................. 11 1 CHAPTER 1: BACKGROUND AND SIGNIFICANCE .................................................. 13 1.1 Type II diabetes: An introduction ..................................................................................................... 14 1.2 Overview of Insulin Action on Glucose Homeostasis ........................................................................ 16 1.2.1 Insulin ............................................................................................................................................... 16 1.2.2 Insulin Secretion ............................................................................................................................... 19 1.2.3 Insulin Signaling ............................................................................................................................... 21 1.2.4 Glucose homeostasis ....................................................................................................................... 22 1.3 Genetics of Type 2 diabetes .............................................................................................................. 25 1.3.1 Genetic studies in humans ............................................................................................................... 26 1.3.2 Missing Heritability ......................................................................................................................... 30 1.3.3 Genetic studies in mouse models .................................................................................................... 32 1. Spontaneous mutant mouse models of T2D ............................................................................... 32 2. Single gene Knock-out and transgenic models of T2D ................................................................. 33 3. Inbred strains (mouse models of polygenic T2D) ........................................................................ 36 1.4 C57BL/6J and A/J Inbred Strains: Alternative model ........................................................................ 38 1.4.1 Advantage of B6 and A/J inbred strains ........................................................................................... 38 1.4.2 B6-chrA CSS development and advantage ........................................................................................ 40 1.4.3 Choosing CSS-6 ................................................................................................................................. 45 1.6 Summary and Research Aims ........................................................................................................... 46 2 CHAPTER 2: INCREASED MITOCHONDRIAL OXIDATIVE PHOSPHORYLATION IN THE LIVER IS ASSOCIATED WITH OBESITY AND INSULIN RESISTANCE ............................................................................................................ 49 2.1 Abstract ............................................................................................................................................ 50 2.2 Introduction ..................................................................................................................................... 52 4 2.3 Materials and Methods .................................................................................................................... 54 2.3.1 Mice. ................................................................................................................................................ 54 2.3.2 RNA Isolation. ................................................................................................................................... 54 2.3.3 Microarray hybridization. ................................................................................................................ 55 2.3.4 Microarray data analysis. ................................................................................................................. 55 2.3.5 Glucose tolerance test (GTT) and insulin secretion ......................................................................... 55 2.3.6 Insulin tolerance test (ITT). .............................................................................................................. 56 2.3.7 Statistics. .......................................................................................................................................... 56 2.4 Results .............................................................................................................................................. 57 2.4.1 Localization of Obrq2 to a 30 Mb interval on chromosome 6 ......................................................... 57 2.4.2 6C1 mice are insulin resistant relative to 6C2 .................................................................................. 59 2.4.3 Global gene expression analysis ...................................................................................................... 61 2.4.4 Genes involved in oxidative phosphorylation are over-expressed in the liver of 6C1 ..................... 63 2.5 Discussion ........................................................................................................................................ 67 3 CHAPTER 3: SOLUTE RECEPTOR SLC35B4 OVER-EXPRESSION LINKED TO DIET-INDUCED OBESITY AND INSULIN RESISTANCE ................................................. 74 3.1 Abstract ............................................................................................................................................ 75 3.2 Introduction ..................................................................................................................................... 77 3.3 Materials and Methods .................................................................................................................... 80 3.3.1 Husbandry ........................................................................................................................................ 80 3.3.2 Generation of subcongenic and subsubcongenic strains ................................................................. 80 3.3.3 Sequence Analysis. ........................................................................................................................... 81 3.3.4 Fasting insulin, fasting glucose and HOMA-IR .................................................................................. 81 3.3.5 Glucose Tolerance Test. ................................................................................................................... 82 3.3.6 Tissue Collection and RNA extraction .............................................................................................. 82 3.3.7 Real-time quantitative PCR. ............................................................................................................. 82 3.3.8 Hyperinsulinemic-Euglycemic Clamp. .............................................................................................. 82 3.3.9 Determination of glucose uptake in peripheral tissues. .................................................................. 84 3.3.10 Statistics. ........................................................................................................................................ 85 3.4 Results ............................................................................................................................................. 85 3.4.1 Obrq2a regulates body weight and IR ............................................................................................
Load more

Recommended publications
  • Epigenetic Silencing of TGFBI Confers Resistance to Trastuzumab in Human Breast Cancer
    Palomeras et al. Breast Cancer Research (2019) 21:79 https://doi.org/10.1186/s13058-019-1160-x RESEARCH ARTICLE Open Access Epigenetic silencing of TGFBI confers resistance to trastuzumab in human breast cancer Sònia Palomeras1†, Ángel Diaz-Lagares2,3†, Gemma Viñas1,4,5, Fernando Setien2, Humberto J. Ferreira2, Glòria Oliveras1,6, Ana B. Crujeiras7,8, Alejandro Hernández4, David H. Lum9, Alana L. Welm9, Manel Esteller2,10,11,12,13* and Teresa Puig1* Abstract Background: Acquired resistance to trastuzumab is a major clinical problem in the treatment of HER2-positive (HER2+) breast cancer patients. The selection of trastuzumab-resistant patients is a great challenge of precision oncology. The aim of this study was to identify novel epigenetic biomarkers associated to trastuzumab resistance in HER2+ BC patients. Methods: We performed a genome-wide DNA methylation (450K array) and a transcriptomic analysis (RNA-Seq) comparing trastuzumab-sensitive (SK) and trastuzumab-resistant (SKTR) HER2+ human breast cancer cell models. The methylation and expression levels of candidate genes were validated by bisulfite pyrosequencing and qRT-PCR, respectively. Functional assays were conducted in the SK and SKTR models by gene silencing and overexpression. Methylation analysis in 24 HER2+ human BC samples with complete response or non-response to trastuzumab- based treatment was conducted by bisulfite pyrosequencing. Results: Epigenomic and transcriptomic analysis revealed the consistent hypermethylation and downregulation of TGFBI, CXCL2, and SLC38A1 genes in association with trastuzumab resistance. The DNA methylation and expression levels of these genes were validated in both sensitive and resistant models analyzed. Of the genes, TGFBI presented the highest hypermethylation-associated silencing both at the transcriptional and protein level.
    [Show full text]
  • 4-6 Weeks Old Female C57BL/6 Mice Obtained from Jackson Labs Were Used for Cell Isolation
    Methods Mice: 4-6 weeks old female C57BL/6 mice obtained from Jackson labs were used for cell isolation. Female Foxp3-IRES-GFP reporter mice (1), backcrossed to B6/C57 background for 10 generations, were used for the isolation of naïve CD4 and naïve CD8 cells for the RNAseq experiments. The mice were housed in pathogen-free animal facility in the La Jolla Institute for Allergy and Immunology and were used according to protocols approved by the Institutional Animal Care and use Committee. Preparation of cells: Subsets of thymocytes were isolated by cell sorting as previously described (2), after cell surface staining using CD4 (GK1.5), CD8 (53-6.7), CD3ε (145- 2C11), CD24 (M1/69) (all from Biolegend). DP cells: CD4+CD8 int/hi; CD4 SP cells: CD4CD3 hi, CD24 int/lo; CD8 SP cells: CD8 int/hi CD4 CD3 hi, CD24 int/lo (Fig S2). Peripheral subsets were isolated after pooling spleen and lymph nodes. T cells were enriched by negative isolation using Dynabeads (Dynabeads untouched mouse T cells, 11413D, Invitrogen). After surface staining for CD4 (GK1.5), CD8 (53-6.7), CD62L (MEL-14), CD25 (PC61) and CD44 (IM7), naïve CD4+CD62L hiCD25-CD44lo and naïve CD8+CD62L hiCD25-CD44lo were obtained by sorting (BD FACS Aria). Additionally, for the RNAseq experiments, CD4 and CD8 naïve cells were isolated by sorting T cells from the Foxp3- IRES-GFP mice: CD4+CD62LhiCD25–CD44lo GFP(FOXP3)– and CD8+CD62LhiCD25– CD44lo GFP(FOXP3)– (antibodies were from Biolegend). In some cases, naïve CD4 cells were cultured in vitro under Th1 or Th2 polarizing conditions (3, 4).
    [Show full text]
  • Familial Cortical Myoclonus Caused by Mutation in NOL3 by Jonathan Foster Rnsseil DISSERTATION Submitted in Partial Satisfaction
    Familial Cortical Myoclonus Caused by Mutation in NOL3 by Jonathan Foster Rnsseil DISSERTATION Submitted in partial satisfaction of the requirements for the degree of DOCTOR OF PHILOSOPHY in Biomedical Sciences in the Copyright 2013 by Jonathan Foster Russell ii I dedicate this dissertation to Mom and Dad, for their adamantine love and support iii No man has earned the right to intellectual ambition until he has learned to lay his course by a star which he has never seen—to dig by the divining rod for springs which he may never reach. In saying this, I point to that which will make your study heroic. For I say to you in all sadness of conviction, that to think great thoughts you must be heroes as well as idealists. Only when you have worked alone – when you have felt around you a black gulf of solitude more isolating than that which surrounds the dying man, and in hope and in despair have trusted to your own unshaken will – then only will you have achieved. Thus only can you gain the secret isolated joy of the thinker, who knows that, a hundred years after he is dead and forgotten, men who never heard of him will be moving to the measure of his thought—the subtile rapture of a postponed power, which the world knows not because it has no external trappings, but which to his prophetic vision is more real than that which commands an army. -Oliver Wendell Holmes, Jr. iv ACKNOWLEDGMENTS I am humbled by the efforts of many, many others who were essential for this work.
    [Show full text]
  • Genome-Wide DNA Methylation Analysis of Human Pancreatic Islets from Type 2 Diabetic and Non-Diabetic Donors Identifies Candidat
    Genome-wide DNA methylation analysis of human pancreatic islets from type 2 diabetic and non-diabetic donors identifies candidate genes that influence insulin secretion. Dayeh, Tasnim; Volkov, Petr; Salö, Sofia; Hall, Elin; Nilsson, Emma A; Olsson, Anders H; Kirkpatrick, Clare L; Wollheim, Claes; Eliasson, Lena; Rönn, Tina; Bacos, Karl; Ling, Charlotte Published in: PLoS Genetics DOI: 10.1371/journal.pgen.1004160 2014 Link to publication Citation for published version (APA): Dayeh, T., Volkov, P., Salö, S., Hall, E., Nilsson, E. A., Olsson, A. H., Kirkpatrick, C. L., Wollheim, C., Eliasson, L., Rönn, T., Bacos, K., & Ling, C. (2014). Genome-wide DNA methylation analysis of human pancreatic islets from type 2 diabetic and non-diabetic donors identifies candidate genes that influence insulin secretion. PLoS Genetics, 10(3), [e1004160]. https://doi.org/10.1371/journal.pgen.1004160 Total number of authors: 12 General rights Unless other specific re-use rights are stated the following general rights apply: Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Read more about Creative commons licenses: https://creativecommons.org/licenses/ Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
    [Show full text]
  • Autocrine IFN Signaling Inducing Profibrotic Fibroblast Responses By
    Downloaded from http://www.jimmunol.org/ by guest on September 23, 2021 Inducing is online at: average * The Journal of Immunology , 11 of which you can access for free at: 2013; 191:2956-2966; Prepublished online 16 from submission to initial decision 4 weeks from acceptance to publication August 2013; doi: 10.4049/jimmunol.1300376 http://www.jimmunol.org/content/191/6/2956 A Synthetic TLR3 Ligand Mitigates Profibrotic Fibroblast Responses by Autocrine IFN Signaling Feng Fang, Kohtaro Ooka, Xiaoyong Sun, Ruchi Shah, Swati Bhattacharyya, Jun Wei and John Varga J Immunol cites 49 articles Submit online. Every submission reviewed by practicing scientists ? is published twice each month by Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://jimmunol.org/subscription Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html http://www.jimmunol.org/content/suppl/2013/08/20/jimmunol.130037 6.DC1 This article http://www.jimmunol.org/content/191/6/2956.full#ref-list-1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material References Permissions Email Alerts Subscription Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2013 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of September 23, 2021. The Journal of Immunology A Synthetic TLR3 Ligand Mitigates Profibrotic Fibroblast Responses by Inducing Autocrine IFN Signaling Feng Fang,* Kohtaro Ooka,* Xiaoyong Sun,† Ruchi Shah,* Swati Bhattacharyya,* Jun Wei,* and John Varga* Activation of TLR3 by exogenous microbial ligands or endogenous injury-associated ligands leads to production of type I IFN.
    [Show full text]
  • Mrna Expression in Human Leiomyoma and Eker Rats As Measured by Microarray Analysis
    Table 3S: mRNA Expression in Human Leiomyoma and Eker Rats as Measured by Microarray Analysis Human_avg Rat_avg_ PENG_ Entrez. Human_ log2_ log2_ RAPAMYCIN Gene.Symbol Gene.ID Gene Description avg_tstat Human_FDR foldChange Rat_avg_tstat Rat_FDR foldChange _DN A1BG 1 alpha-1-B glycoprotein 4.982 9.52E-05 0.68 -0.8346 0.4639 -0.38 A1CF 29974 APOBEC1 complementation factor -0.08024 0.9541 -0.02 0.9141 0.421 0.10 A2BP1 54715 ataxin 2-binding protein 1 2.811 0.01093 0.65 0.07114 0.954 -0.01 A2LD1 87769 AIG2-like domain 1 -0.3033 0.8056 -0.09 -3.365 0.005704 -0.42 A2M 2 alpha-2-macroglobulin -0.8113 0.4691 -0.03 6.02 0 1.75 A4GALT 53947 alpha 1,4-galactosyltransferase 0.4383 0.7128 0.11 6.304 0 2.30 AACS 65985 acetoacetyl-CoA synthetase 0.3595 0.7664 0.03 3.534 0.00388 0.38 AADAC 13 arylacetamide deacetylase (esterase) 0.569 0.6216 0.16 0.005588 0.9968 0.00 AADAT 51166 aminoadipate aminotransferase -0.9577 0.3876 -0.11 0.8123 0.4752 0.24 AAK1 22848 AP2 associated kinase 1 -1.261 0.2505 -0.25 0.8232 0.4689 0.12 AAMP 14 angio-associated, migratory cell protein 0.873 0.4351 0.07 1.656 0.1476 0.06 AANAT 15 arylalkylamine N-acetyltransferase -0.3998 0.7394 -0.08 0.8486 0.456 0.18 AARS 16 alanyl-tRNA synthetase 5.517 0 0.34 8.616 0 0.69 AARS2 57505 alanyl-tRNA synthetase 2, mitochondrial (putative) 1.701 0.1158 0.35 0.5011 0.6622 0.07 AARSD1 80755 alanyl-tRNA synthetase domain containing 1 4.403 9.52E-05 0.52 1.279 0.2609 0.13 AASDH 132949 aminoadipate-semialdehyde dehydrogenase -0.8921 0.4247 -0.12 -2.564 0.02993 -0.32 AASDHPPT 60496 aminoadipate-semialdehyde
    [Show full text]
  • Autocrine IFN Signaling Inducing Profibrotic Fibroblast Responses by a Synthetic TLR3 Ligand Mitigates
    Downloaded from http://www.jimmunol.org/ by guest on September 28, 2021 Inducing is online at: average * The Journal of Immunology published online 16 August 2013 from submission to initial decision 4 weeks from acceptance to publication http://www.jimmunol.org/content/early/2013/08/16/jimmun ol.1300376 A Synthetic TLR3 Ligand Mitigates Profibrotic Fibroblast Responses by Autocrine IFN Signaling Feng Fang, Kohtaro Ooka, Xiaoyong Sun, Ruchi Shah, Swati Bhattacharyya, Jun Wei and John Varga J Immunol Submit online. Every submission reviewed by practicing scientists ? is published twice each month by http://jimmunol.org/subscription Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://www.jimmunol.org/content/suppl/2013/08/20/jimmunol.130037 6.DC1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material Permissions Email Alerts Subscription Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2013 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of September 28, 2021. Published August 16, 2013, doi:10.4049/jimmunol.1300376 The Journal of Immunology A Synthetic TLR3 Ligand Mitigates Profibrotic Fibroblast Responses by Inducing Autocrine IFN Signaling Feng Fang,* Kohtaro Ooka,* Xiaoyong Sun,† Ruchi Shah,* Swati Bhattacharyya,* Jun Wei,* and John Varga* Activation of TLR3 by exogenous microbial ligands or endogenous injury-associated ligands leads to production of type I IFN.
    [Show full text]
  • Molecular Characterization of Ductal Carcinoma in Situ: Pilot Studies Neil Bipinchandra Desai Yale University
    Yale University EliScholar – A Digital Platform for Scholarly Publishing at Yale Yale Medicine Thesis Digital Library School of Medicine 2010 Molecular Characterization of Ductal Carcinoma In Situ: Pilot Studies Neil Bipinchandra Desai Yale University Follow this and additional works at: http://elischolar.library.yale.edu/ymtdl Part of the Medicine and Health Sciences Commons Recommended Citation Desai, Neil Bipinchandra, "Molecular Characterization of Ductal Carcinoma In Situ: Pilot Studies" (2010). Yale Medicine Thesis Digital Library. 153. http://elischolar.library.yale.edu/ymtdl/153 This Open Access Thesis is brought to you for free and open access by the School of Medicine at EliScholar – A Digital Platform for Scholarly Publishing at Yale. It has been accepted for inclusion in Yale Medicine Thesis Digital Library by an authorized administrator of EliScholar – A Digital Platform for Scholarly Publishing at Yale. For more information, please contact [email protected]. Molecular Characterization of Progression in Ductal Carcinoma In Situ: Pilot Studies A Thesis Submitted to the Yale University School of Medicine in Partial Fulfillment of the Requirements of the Degree of Doctor of Medicine by Neil Desai 2010 ! "! Abstract MOLECULAR CHARACTERIZATION OF PROGRESSION IN DUCTAL CARCINOMA IN SITU: PILOT STUDIES Neil B. Desai,1 Arun Gopinath,1 Sebastian Szpakowski,1 Rajini Haraksingh,3 Veerle Bossuyt,1 Michael O. Krauthammer,1 David Tuck,1 Donald R. Lannin,2 and David F. Stern.1 1Department of Pathology, Yale University, School of Medicine,
    [Show full text]
  • Functional Consequences of Setd1a Haploinsufficiency: from Gestation to Behaviour
    Functional consequences of Setd1a haploinsufficiency: from gestation to behaviour by Matthew Lee Bosworth A thesis submitted for the degree of Doctor of Philosophy September 2019 Declarations Statement 1 This thesis is being submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy. ____________________________ (Matthew Bosworth) Date 24/09/2019 Statement 2 This work has not been submitted in substance for any other degree or award at this or any other university or place of learning, nor is it being submitted concurrently for any other degree or award (outside of any formal collaboration agreement between the University and a partner organisation) ____________________________ (Matthew Bosworth) Date 24/09/2019 Statement 3 I hereby give consent for my thesis, if accepted, to be available in the University’s Open Access repository (or, where approved, to be available in the University's library and for inter-library loan), and for the title and summary to be made available to outside organisations, subject to the expiry of a University-approved bar on access if applicable. ____________________________ (Matthew Bosworth) Date 24/09/2019 Declaration This thesis is the result of my own independent work, except where otherwise stated, and the views expressed are my own. Other sources are acknowledged by explicit references. The thesis has not been edited by a third party beyond what is permitted by Cardiff University's Use of Third Party Editors by Research Degree Students Procedure. ____________________________ (Matthew Bosworth) Date 24/09/2019 i ii Summary Advances in psychiatric genetics are providing opportunities to investigate underlying pathogenic mechanisms.
    [Show full text]
  • Exoc3l (G-13): Sc-136667
    SAN TA C RUZ BI OTEC HNOL OG Y, INC . ExoC3L (G-13): sc-136667 BACKGROUND APPLICATIONS ExoC3L (exocyst complex component 3-like protein), also known as protein ExoC3L (G-13) is recommended for detection of ExoC3L of mouse, rat and jiangli, is a 746 amino acid protein that belongs to the SEC6 family. Localizing human origin by Western Blotting (starting dilution 1:100, dilution range to the cytoplasmic and secretory vesicle, ExoC3L colocalizes with Insulin 1:50-1:500), immunoprecipitation [1-2 µg per 100-500 µg of total protein granules and interacts with ExoC2, ExoC4 and ExoC5. Acting as part of the (1 ml of cell lysate)], immunofluorescence (starting dilution 1:25, dilution exocyst, ExoC3L may function in the regulation of Insulin granule exocytosis range 1:25-1:250) and solid phase ELISA (starting dilution 1:30, dilution and is expressed in Insulin-secreting MIN6 cells, as well as various tissues range 1:30-1:3000); non cross-reactive with ExoC3L2. including brain and pancreatic islets. The gene encoding ExoC3L maps to ExoC3L (G-13) is also recommended for detection of ExoC3L in additional human chromosome 16, which encodes over 900 genes and comprises nearly species, including canine, bovine and porcine. 3% of the human genome. The GAN gene is located on chromosome 16 and, with mutation, may lead to giant axonal neuropathy, a nervous system disor - Suitable for use as control antibody for ExoC3L siRNA (h): sc-93361, ExoC3L der characterized by increasing malfunction with growth. The rare disorder siRNA (m): sc-144971, ExoC3L shRNA Plasmid (h): sc-93361-SH, ExoC3L Rubinstein-Taybi syndrome is also associated with chromosome 16, as is shRNA Plasmid (m): sc-144971-SH, ExoC3L shRNA (h) Lentiviral Particles: Crohn’s disease, which is a gastrointestinal inflammatory condition.
    [Show full text]
  • Expression, Prognosis, and Immune Infiltrates Analyses of E2fs in Human Brain and CNS Cancer
    Hindawi BioMed Research International Volume 2020, Article ID 6281635, 17 pages https://doi.org/10.1155/2020/6281635 Research Article Expression, Prognosis, and Immune Infiltrates Analyses of E2Fs in Human Brain and CNS Cancer Pan Liao,1 Shuzhen Han ,2 and Honglan Qu 3 1Inner Mongolia University for the Nationalities, Tongliao, China 2Department of Neurology, Inner Mongolia Forestry General Hospital, Yakeshi, Inner Mongolia, China 3Department of Oncology, Inner Mongolia Forestry General Hospital, Yakeshi, Inner Mongolia, China Correspondence should be addressed to Shuzhen Han; [email protected] and Honglan Qu; [email protected] Received 23 April 2020; Accepted 6 August 2020; Published 15 December 2020 Academic Editor: Bilal Alatas Copyright © 2020 Pan Liao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objective. We investigated the expression patterns, potential functions, unique prognostic value, and potential therapeutic targets of E2Fs in brain and CNS cancer and tumor-infiltrating immune cell microenvironments. Methods. We analyzed E2F mRNA expression levels in diverse cancer types via Oncomine and GEPIA databases, respectively. Moreover, we evaluated the prognostic values using GEPIA database and TCGAportal database and the correlation of E2F expression with immune infiltration and the correlation between immune cell infiltration and GBM and LGG prognosis via TIMER database. Then, cBioPortal, GeneMANIA, and DAVID databases were used for mutation analysis, PPI network analysis of coexpressed gene, and functional enrichment analysis. Results. E2F1-8 expression increased in most cancers, including brain and CNS cancer. Higher expression in E2F1, 2, 4, 6, 7, and 8 indicated poor OS of LGG.
    [Show full text]
  • 1 Imipramine Treatment and Resiliency Exhibit Similar
    Imipramine Treatment and Resiliency Exhibit Similar Chromatin Regulation in the Mouse Nucleus Accumbens in Depression Models Wilkinson et al. Supplemental Material 1. Supplemental Methods 2. Supplemental References for Tables 3. Supplemental Tables S1 – S24 SUPPLEMENTAL TABLE S1: Genes Demonstrating Increased Repressive DimethylK9/K27-H3 Methylation in the Social Defeat Model (p<0.001) SUPPLEMENTAL TABLE S2: Genes Demonstrating Decreased Repressive DimethylK9/K27-H3 Methylation in the Social Defeat Model (p<0.001) SUPPLEMENTAL TABLE S3: Genes Demonstrating Increased Repressive DimethylK9/K27-H3 Methylation in the Social Isolation Model (p<0.001) SUPPLEMENTAL TABLE S4: Genes Demonstrating Decreased Repressive DimethylK9/K27-H3 Methylation in the Social Isolation Model (p<0.001) SUPPLEMENTAL TABLE S5: Genes Demonstrating Common Altered Repressive DimethylK9/K27-H3 Methylation in the Social Defeat and Social Isolation Models (p<0.001) SUPPLEMENTAL TABLE S6: Genes Demonstrating Increased Repressive DimethylK9/K27-H3 Methylation in the Social Defeat and Social Isolation Models (p<0.001) SUPPLEMENTAL TABLE S7: Genes Demonstrating Decreased Repressive DimethylK9/K27-H3 Methylation in the Social Defeat and Social Isolation Models (p<0.001) SUPPLEMENTAL TABLE S8: Genes Demonstrating Increased Phospho-CREB Binding in the Social Defeat Model (p<0.001) SUPPLEMENTAL TABLE S9: Genes Demonstrating Decreased Phospho-CREB Binding in the Social Defeat Model (p<0.001) SUPPLEMENTAL TABLE S10: Genes Demonstrating Increased Phospho-CREB Binding in the Social
    [Show full text]