Comparison of Genes Expressed in Primed States of Human And
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
ACTL6A Promotes the Proliferation of Esophageal Squamous Cell Carcinoma Cells and Correlates with Poor Clinical Outcomes
OncoTargets and Therapy Dovepress open access to scientific and medical research Open Access Full Text Article ORIGINAL RESEARCH ACTL6A Promotes the Proliferation of Esophageal Squamous Cell Carcinoma Cells and Correlates with Poor Clinical Outcomes This article was published in the following Dove Press journal: OncoTargets and Therapy Rui-zhe Li1 Background: ACTL6A, a regulatory subunit of ATP-dependent chromatin-remodeling Yun-yun Li1,2 complexes SWI/SNF, has been identified as a central oncogenic driver in many tumor types. Hui Qin1 Materials and Methods: We used immunohistochemistry (IHC) to detect ACTL6A Shan-shan Li1 expression in esophageal squamous cell carcinoma (ESCC) tissues. Then, the effect of ACTL6A on proliferation and DNA synthesis was explored by using cell counting kit 8 1 Department of Pathology, School of (CCK8) and EdU retention assays. The potential oncogenic mechanism of ACTL6A in Basic Medical Sciences, Zhengzhou University and First Affiliated Hospital of ESCC cells was also analyzed by flow cytometry and Western blotting. We further estab Zhengzhou University, Zhengzhou, lished an ESCC xenograft mouse model to validate the in vitro results. Henan 450000, People’s Republic of China; 2Department of Stomatology, First Results: ACTL6A expression, localized in cancer cell nuclei, was markedly higher in ESCC Affiliated Hospital of Zhengzhou tissues than in the corresponding noncancerous tissues (P<0.001) and was positively asso University, Zhengzhou, Henan 450000, ciated with tumor size, histological differentiation, T stage and tumor-node-metastasis People’s Republic of China (TNM) stage. Kaplan–Meier analysis revealed that high ACTL6A expression was signifi cantly associated with poor overall survival (OS) (P = 0.008, HR= 2.562, 95% CI: 1.241– 5.289), and decision curve analysis (DCA) demonstrated that ACTL6A could increase the clinical prognostic efficiency of the original clinical prediction model. -
Mouse Germ Line Mutations Due to Retrotransposon Insertions Liane Gagnier1, Victoria P
Gagnier et al. Mobile DNA (2019) 10:15 https://doi.org/10.1186/s13100-019-0157-4 REVIEW Open Access Mouse germ line mutations due to retrotransposon insertions Liane Gagnier1, Victoria P. Belancio2 and Dixie L. Mager1* Abstract Transposable element (TE) insertions are responsible for a significant fraction of spontaneous germ line mutations reported in inbred mouse strains. This major contribution of TEs to the mutational landscape in mouse contrasts with the situation in human, where their relative contribution as germ line insertional mutagens is much lower. In this focussed review, we provide comprehensive lists of TE-induced mouse mutations, discuss the different TE types involved in these insertional mutations and elaborate on particularly interesting cases. We also discuss differences and similarities between the mutational role of TEs in mice and humans. Keywords: Endogenous retroviruses, Long terminal repeats, Long interspersed elements, Short interspersed elements, Germ line mutation, Inbred mice, Insertional mutagenesis, Transcriptional interference Background promoter and polyadenylation motifs and often a splice The mouse and human genomes harbor similar types of donor site [10, 11]. Sequences of full-length ERVs can TEs that have been discussed in many reviews, to which encode gag, pol and sometimes env, although groups of we refer the reader for more in depth and general infor- LTR retrotransposons with little or no retroviral hom- mation [1–9]. In general, both human and mouse con- ology also exist [6–9]. While not the subject of this re- tain ancient families of DNA transposons, none view, ERV LTRs can often act as cellular enhancers or currently active, which comprise 1–3% of these genomes promoters, creating chimeric transcripts with genes, and as well as many families or groups of retrotransposons, have been implicated in other regulatory functions [11– which have caused all the TE insertional mutations in 13]. -
Efficacy and Mechanistic Evaluation of Tic10, a Novel Antitumor Agent
University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2012 Efficacy and Mechanisticv E aluation of Tic10, A Novel Antitumor Agent Joshua Edward Allen University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Oncology Commons Recommended Citation Allen, Joshua Edward, "Efficacy and Mechanisticv E aluation of Tic10, A Novel Antitumor Agent" (2012). Publicly Accessible Penn Dissertations. 488. https://repository.upenn.edu/edissertations/488 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/488 For more information, please contact [email protected]. Efficacy and Mechanisticv E aluation of Tic10, A Novel Antitumor Agent Abstract TNF-related apoptosis-inducing ligand (TRAIL; Apo2L) is an endogenous protein that selectively induces apoptosis in cancer cells and is a critical effector in the immune surveillance of cancer. Recombinant TRAIL and TRAIL-agonist antibodies are in clinical trials for the treatment of solid malignancies due to the cancer-specific cytotoxicity of TRAIL. Recombinant TRAIL has a short serum half-life and both recombinant TRAIL and TRAIL receptor agonist antibodies have a limited capacity to perfuse to tissue compartments such as the brain, limiting their efficacy in certain malignancies. To overcome such limitations, we searched for small molecules capable of inducing the TRAIL gene using a high throughput luciferase reporter gene assay. We selected TRAIL-inducing compound 10 (TIC10) for further study based on its induction of TRAIL at the cell surface and its promising therapeutic index. TIC10 is a potent, stable, and orally active antitumor agent that crosses the blood-brain barrier and transcriptionally induces TRAIL and TRAIL-mediated cell death in a p53-independent manner. -
Molecular Mechanisms Involved Involved in the Interaction Effects of HCV and Ethanol on Liver Cirrhosis
Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2010 Molecular Mechanisms Involved Involved in the Interaction Effects of HCV and Ethanol on Liver Cirrhosis Ryan Fassnacht Virginia Commonwealth University Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Physiology Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/2246 This Thesis is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. Ryan C. Fassnacht 2010 All Rights Reserved Molecular Mechanisms Involved in the Interaction Effects of HCV and Ethanol on Liver Cirrhosis A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University. by Ryan Christopher Fassnacht, B.S. Hampden Sydney University, 2005 M.S. Virginia Commonwealth University, 2010 Director: Valeria Mas, Ph.D., Associate Professor of Surgery and Pathology Division of Transplant Department of Surgery Virginia Commonwealth University Richmond, Virginia July 9, 2010 Acknowledgement The Author wishes to thank his family and close friends for their support. He would also like to thank the members of the molecular transplant team for their help and advice. This project would not have been possible with out the help of Dr. Valeria Mas and her endearing -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Protein Identities in Evs Isolated from U87-MG GBM Cells As Determined by NG LC-MS/MS
Protein identities in EVs isolated from U87-MG GBM cells as determined by NG LC-MS/MS. No. Accession Description Σ Coverage Σ# Proteins Σ# Unique Peptides Σ# Peptides Σ# PSMs # AAs MW [kDa] calc. pI 1 A8MS94 Putative golgin subfamily A member 2-like protein 5 OS=Homo sapiens PE=5 SV=2 - [GG2L5_HUMAN] 100 1 1 7 88 110 12,03704523 5,681152344 2 P60660 Myosin light polypeptide 6 OS=Homo sapiens GN=MYL6 PE=1 SV=2 - [MYL6_HUMAN] 100 3 5 17 173 151 16,91913397 4,652832031 3 Q6ZYL4 General transcription factor IIH subunit 5 OS=Homo sapiens GN=GTF2H5 PE=1 SV=1 - [TF2H5_HUMAN] 98,59 1 1 4 13 71 8,048185945 4,652832031 4 P60709 Actin, cytoplasmic 1 OS=Homo sapiens GN=ACTB PE=1 SV=1 - [ACTB_HUMAN] 97,6 5 5 35 917 375 41,70973209 5,478027344 5 P13489 Ribonuclease inhibitor OS=Homo sapiens GN=RNH1 PE=1 SV=2 - [RINI_HUMAN] 96,75 1 12 37 173 461 49,94108966 4,817871094 6 P09382 Galectin-1 OS=Homo sapiens GN=LGALS1 PE=1 SV=2 - [LEG1_HUMAN] 96,3 1 7 14 283 135 14,70620005 5,503417969 7 P60174 Triosephosphate isomerase OS=Homo sapiens GN=TPI1 PE=1 SV=3 - [TPIS_HUMAN] 95,1 3 16 25 375 286 30,77169764 5,922363281 8 P04406 Glyceraldehyde-3-phosphate dehydrogenase OS=Homo sapiens GN=GAPDH PE=1 SV=3 - [G3P_HUMAN] 94,63 2 13 31 509 335 36,03039959 8,455566406 9 Q15185 Prostaglandin E synthase 3 OS=Homo sapiens GN=PTGES3 PE=1 SV=1 - [TEBP_HUMAN] 93,13 1 5 12 74 160 18,68541938 4,538574219 10 P09417 Dihydropteridine reductase OS=Homo sapiens GN=QDPR PE=1 SV=2 - [DHPR_HUMAN] 93,03 1 1 17 69 244 25,77302971 7,371582031 11 P01911 HLA class II histocompatibility antigen, -
Browsing Genes and Genomes with Ensembl
The Bioinformatics Roadshow Tórshavn, The Faroe Islands 28-29 November 2012 BROWSING GENES AND GENOMES WITH ENSEMBL EXERCISES AND ANSWERS 1 BROWSER 3 BIOMART 8 VARIATION 13 COMPARATIVE GENOMICS 18 2 Note: These exercises are based on Ensembl version 69 (October 2012). After in future a new version has gone live, version 69 will still be available at http://e69.ensembl.org/. If your answer doesn’t correspond with the given answer, please consult the instructor. ______________________________________________________________ BROWSER ______________________________________________________________ Exercise 1 – Exploring a gene (a) Find the human F9 (coagulation factor IX) gene. On which chromosome and which strand of the genome is this gene located? How many transcripts (splice variants) have been annotated for it? (b) What is the longest transcript? How long is the protein it encodes? Has this transcript been annotated automatically (by Ensembl) or manually (by Havana)? How many exons does it have? Are any of the exons completely or partially untranslated? (c) Have a look at the external references for ENST00000218099. What is the function of F9? (d) Is it possible to monitor expression of ENST00000218099 with the ILLUMINA HumanWG_6_V2 microarray? If so, can it also be used to monitor expression of the other two transcripts? (e) In which part (i.e. the N-terminal or C-terminal half) of the protein encoded by ENST00000218099 does its peptidase activity reside? (f) Have any missense variants been discovered for the protein encoded by ENST00000218099? (g) Is there a mouse orthologue predicted for the human F9 gene? (h) If you have yourself a gene of interest, explore what information Ensembl displays about it! ______________________________________________________________ Answer (a) 8 Go to the Ensembl homepage (http://www.ensembl.org/). -
Increased ACTL6A Occupancy Within Mswi/SNF Chromatin Remodelers
bioRxiv preprint doi: https://doi.org/10.1101/2021.03.22.435873; this version posted March 22, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Increased ACTL6A Occupancy Within mSWI/SNF Chromatin Remodelers Drives Human Squamous Cell Carcinoma Chiung-Ying Chang1,2,7, Zohar Shipony3,7, Ann Kuo1,2, Kyle M. Loh4,5, William J. Greenleaf3,6, Gerald R. Crabtree1,2,5* 1Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA. 2Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA. 3Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA. 4Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA. 5Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, USA. 6Department of Applied Physics, Stanford University, Stanford, California 94305, USA. 7These authors contributed equally. *Corresponding author: Gerald R. Crabtree, [email protected] Summary Mammalian SWI/SNF (BAF) chromatin remodelers play dosage-sensitive roles in many human malignancies and neurologic disorders. The gene encoding the BAF subunit, ACTL6A, is amplified at an early stage in the development of squamous cell carcinomas (SCCs), but its oncogenic role remains unclear. Here we demonstrate that ACTL6A overexpression leads to its stoichiometric assembly into BAF complexes and drives its interaction and engagement with specific regulatory regions in the genome. In normal epithelial cells, ACTL6A was sub-stoichiometric to other BAF subunits. However, increased ACTL6A levels by ectopic expression or in SCC cells led to near-saturation of ACTL6A within BAF complexes. -
Open Full Page
Published OnlineFirst August 15, 2016; DOI: 10.1158/1078-0432.CCR-16-0290 Biology of Human Tumors Clinical Cancer Research Recurrent TRIO Fusion in Nontranslocation– Related Sarcomas Lucile Delespaul1,2, Tom Lesluyes1,2,Gaelle€ Perot 1,3,Celine Brulard1, Lydia Lartigue1,2, Jessica Baud1,2, Pauline Lagarde1, Sophie Le Guellec4,Agnes Neuville1,3, Philippe Terrier5, Dominique Vince-Ranchere 6, Susanne Schmidt7, Anne Debant7, Jean-Michel Coindre1,2,3, and Fred eric Chibon1,3 Abstract Purpose: Despite various differences, nontranslocation-related with various partners, was identified in 5.1% of cases. TRIO sarcomas (e.g., comprising undifferentiated pleomorphic sarcoma, translocations are either intrachromosomal with TERT or inter- leiomyosarcoma, myxofibrosarcoma) are unified by their complex chromosomal with LINC01504 or ZNF558. Our results suggest genetics. Extensive analysis of the tumor genome using molecular that all translocations led to a truncated TRIO protein either cytogenetic approaches showed many chromosomal gains, losses, directly or indirectly by alternative splicing. TRIO rearrangement and translocations per cell. Genomic quantitative alterations and is associated with a modified transcriptomic program to immu- expression variations have been extensively studied by adapted nity/inflammation, proliferation and migration, and an increase high-throughput approaches, yet translocations still remained in proliferation. unscreened. We therefore analyzed 117 nontranslocation-related Conclusions: TRIO fusions have been identified in four -
Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase -
Expressed Gene Fusions As Frequent Drivers of Poor Outcomes in Hormone Receptor–Positive Breast Cancer
Published OnlineFirst December 14, 2017; DOI: 10.1158/2159-8290.CD-17-0535 RESEARCH ARTICLE Expressed Gene Fusions as Frequent Drivers of Poor Outcomes in Hormone Receptor–Positive Breast Cancer Karina J. Matissek1,2, Maristela L. Onozato3, Sheng Sun1,2, Zongli Zheng2,3,4, Andrew Schultz1, Jesse Lee3, Kristofer Patel1, Piiha-Lotta Jerevall2,3, Srinivas Vinod Saladi1,2, Allison Macleay3, Mehrad Tavallai1,2, Tanja Badovinac-Crnjevic5, Carlos Barrios6, Nuran Beşe7, Arlene Chan8, Yanin Chavarri-Guerra9, Marcio Debiasi6, Elif Demirdögen10, Ünal Egeli10, Sahsuvar Gökgöz10, Henry Gomez11, Pedro Liedke6, Ismet Tasdelen10, Sahsine Tolunay10, Gustavo Werutsky6, Jessica St. Louis1, Nora Horick12, Dianne M. Finkelstein2,12, Long Phi Le2,3, Aditya Bardia1,2, Paul E. Goss1,2, Dennis C. Sgroi2,3, A. John Iafrate2,3, and Leif W. Ellisen1,2 ABSTRACT We sought to uncover genetic drivers of hormone receptor–positive (HR+) breast cancer, using a targeted next-generation sequencing approach for detecting expressed gene rearrangements without prior knowledge of the fusion partners. We identified inter- genic fusions involving driver genes, including PIK3CA, AKT3, RAF1, and ESR1, in 14% (24/173) of unselected patients with advanced HR+ breast cancer. FISH confirmed the corresponding chromo- somal rearrangements in both primary and metastatic tumors. Expression of novel kinase fusions in nontransformed cells deregulates phosphoprotein signaling, cell proliferation, and survival in three- dimensional culture, whereas expression in HR+ breast cancer models modulates estrogen-dependent growth and confers hormonal therapy resistance in vitro and in vivo. Strikingly, shorter overall survival was observed in patients with rearrangement-positive versus rearrangement-negative tumors. Cor- respondingly, fusions were uncommon (<5%) among 300 patients presenting with primary HR+ breast cancer. -
Nuclear PTEN Safeguards Pre-Mrna Splicing to Link Golgi Apparatus for Its Tumor Suppressive Role
ARTICLE DOI: 10.1038/s41467-018-04760-1 OPEN Nuclear PTEN safeguards pre-mRNA splicing to link Golgi apparatus for its tumor suppressive role Shao-Ming Shen1, Yan Ji2, Cheng Zhang1, Shuang-Shu Dong2, Shuo Yang1, Zhong Xiong1, Meng-Kai Ge1, Yun Yu1, Li Xia1, Meng Guo1, Jin-Ke Cheng3, Jun-Ling Liu1,3, Jian-Xiu Yu1,3 & Guo-Qiang Chen1 Dysregulation of pre-mRNA alternative splicing (AS) is closely associated with cancers. However, the relationships between the AS and classic oncogenes/tumor suppressors are 1234567890():,; largely unknown. Here we show that the deletion of tumor suppressor PTEN alters pre-mRNA splicing in a phosphatase-independent manner, and identify 262 PTEN-regulated AS events in 293T cells by RNA sequencing, which are associated with significant worse outcome of cancer patients. Based on these findings, we report that nuclear PTEN interacts with the splicing machinery, spliceosome, to regulate its assembly and pre-mRNA splicing. We also identify a new exon 2b in GOLGA2 transcript and the exon exclusion contributes to PTEN knockdown-induced tumorigenesis by promoting dramatic Golgi extension and secretion, and PTEN depletion significantly sensitizes cancer cells to secretion inhibitors brefeldin A and golgicide A. Our results suggest that Golgi secretion inhibitors alone or in combination with PI3K/Akt kinase inhibitors may be therapeutically useful for PTEN-deficient cancers. 1 Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China. 2 Institute of Health Sciences, Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences and SJTU-SM, Shanghai 200025, China.