DOCSLIB.ORG

Comparative Proteomic Analysis Uncovers Potential Biomarkers Involved in the Anticancer Effect of Scutellarein in Human Gastric Cancer Cells

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Comparative Proteomic Analysis Uncovers Potential Biomarkers Involved in the Anticancer Effect of Scutellarein in Human Gastric Cancer Cells ONCOLOGY REPORTS 44: 939-958, 2020 Comparative proteomic analysis uncovers potential biomarkers involved in the anticancer effect of Scutellarein in human gastric cancer cells VENU VENKATARAME GOWDA SARALAMMA1,2, PREETHI VETRIVEL1, HO JEONG LEE3, SEONG MIN KIM1, SANG EUN HA1, RAJESWARI MURUGESAN4, EUN HEE KIM5, JEONG DOO HEO3 and GON SUP KIM1 1Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongnam 52828; 2College of Pharmacy, Yonsei University, Incheon 21983; 3Gyeongnam Department of Environment Toxicology and Chemistry, Biological Resources Research Group, Korea Institute of Toxicology, Jinju, Gyeongnam 52834, Republic of Korea; 4Department of Biochemistry, Biotechnology and Bioinformatics, Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore, Tamil Nadu 641043, India; 5Department of Nursing Science, International University of Korea, Jinju, Gyeongnam 52833, Republic of Korea Received December 19, 2019; Accepted May 28, 2020 DOI: 10.3892/or.2020.7677 Abstract. Scutellarein (SCU), a flavone that belongs to the studies also confirmed the binding affinity of SCU towards flavonoid family and abundantly present in Scutellaria these critical proteins. Phosphatidylinositol 4,5‑bisphosphate baicalensis a flowering plant in the family Lamiaceae, has been 3‑kinase catalytic subunit β isoform (PIK3CB) protein expres- reported to exhibit anticancer effects in several cancer cell lines sion was accompanied by a distinct group of cellular functions, including gastric cancer (GC). Although our previous study including cell growth, and proliferation. Cancerous inhibitor documented the mechanisms of Scutellarein‑induced cyto- of protein phosphatase 2A (CIP2A), is one of the oncogenic toxic effects, the literature shows that the proteomic changes molecules that have been shown to promote tumor growth that are associated with the cellular response to SCU have been and resistance to apoptosis and senescence‑inducing thera- poorly understood. To avoid adverse side‑effects and signifi- pies. In the present study, both PIK3CB and CIP2A proteins cant toxicity of chemotherapy in patients who react poorly, were downregulated in SCU‑treated cells, which boosts our biomarkers anticipating therapeutic responses are imperative. previous results of SCU to induce apoptosis and inhibits GC In the present study, we utilized a comparative proteomic cell growth by regulating these critical proteins. The compara- analysis to identify proteins associated with Scutellarein tive proteomic analysis has yielded candidate biomarkers of (SCU)‑induced cell death in GC cells (AGS and SNU484), by response to SCU treatment in GC cell models and further integrating two‑dimensional gel electrophoresis (2‑DE), mass validation of these biomarkers will help the future clinical spectrometry (MS), and bioinformatics to analyze the proteins. development of SCU as a novel therapeutic drug. Proteomic analysis between SCU‑treated and DMSO (control) samples successfully identified 41 (AGS) and 31 (SNU484) Introduction proteins by MALDI‑TOF/MS analysis and protein database search. Comparative proteomics analysis between AGS and Gastric cancer was the fifth most prevalent malignancy in 2018 SNU484 cells treated with SCU revealed a total of 7 protein globally with an estimated 1 million new cases. Korea has been identities commonly expressed and western blot analysis listed first among the global GC cases, with stomach cancer validated a subset of identified critical proteins, which were incidence rates in men of approximately 58 per 100,000 and in consistent with those of the 2‑DE outcome. Molecular docking women of 24 per every 100,000, which is an unfortunate reality for many Koreans (1). Epigenetic alterations, aberrant molec- ular signaling pathways, and multiple genetic mutations are engaged in the development of GC (2). Substantial advances in Correspondence to: Professor Gon Sup Kim, Research Institute diagnostic techniques, chemotherapy and surgical approaches, of Life Science and College of Veterinary Medicine, Gyeongsang treatment by multidisciplinary teams and the advancement National University, 501 Jinju‑daero, Jinju, Gyeongnam 52828, of novel therapeutic agents have shown minor improvement Republic of Korea in survival rate in recent times (3). If we can identify the E‑mail: [email protected] biomarkers of drug treatment responses and their efficacy, the unnecessary burden of adverse effects and noticeable toxicity Key words: biomarkers, gastric cancer, scutellarein, from chemotherapy on GC patients unlikely to respond can be two‑dimensional gel electrophoresis, CIP2A, PIK3CB averted (4). It is imperative to identify the specific biomarkers and unique molecular patterns of the tumor to develop treat- ments that target the distinct tumor behavior. In the standard 940 SARALAMMA et al: PROTEIN PROFILING OF GC CELLS TREATED WITH SCUTELLAREIN treatment of GC, a significant number of novel anticancer Materials and methods agents targeting dysfunctional molecular signaling pathways has been reported already, whereas others remain elusive (5,6). Cell lines, reagents and antibodies. Human GC cell lines, The global proteomic approach is one of the computational AGS and SNU484, were procured from the Korea Cell technologies that have been improved in recent times over Line Bank (Seoul, Korea). Antibiotics (penicillin/strepto- many other complementary techniques that briskly change our mycin), fetal bovine serum (FBS) and RPMI‑1640 growth approach to cancer research (7). This empowers scientists to medium were purchased from Gibco, Thermo Fisher screen substantial numbers of proteins within clinical discrete Scientific, Inc. Compound Scutellarein was procured samples, as well as different cell lines treated with specific from Chengdu Biopurify Phytochemicals Ltd. (product drugs that help to analyze and confirm drug targets, find new no. 611130). Chemicals and materials utilized for electro- disease biomarkers, design more adequate drugs, and estimate phoresis were procured from Bio‑Rad Laboratories, Inc. drug efficacy (8). The conventional proteomics approach was 3‑(4,5‑Dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide achieved by implementing a combination of 2‑DE coupled with (MTT) was purchased from Duchefa Biochemie. Antibodies differential image analysis and protein identification using mass for CIP2A (#148053) and PI3KCB (#3011S) were purchased spectrometry (MALDI‑TOF; matrix‑assisted laser desorption/ from Cell Signaling Technology, Inc. OFD1 (#ab222837), ionization‑time of flight) and bioinformatics to predominantly VCL (#ab129002), and HIP1R (#ab226197) antibodies were identify and characterize proteins in the tissues and cells purchased from Abcam. The β‑actin (#MABT825) antibody from both in‑vitro and in‑vivo models (8,9). Protein network, was purchased from Millipore. functional interpretation, and pathway analysis tools can help to address the difficulties in the illustration of the obtained Treatment of SCU and determination of cell viability. proteomics data. To identify the activated pathway element Mycoplasma‑free AGS and SNU484 cells were cultured in of functional proteomic data, the analysis of proteomic data RPMI‑1640 medium containing 10% FBS (heat activated) and at the pathway level has become universally popular (10). The 1% antibiotics (penicillin/streptomycin) in an incubator with comparative proteomic analysis could persuade the molecular 5% CO2 at 37˚C in a humidified condition. To confirm myco- characterization of cellular events correlated with cancer devel- plasma contamination, we used the e‑Myco™ Mycoplasma opmental, signaling, and progression phases that leads to the PCR Detection kit (iNtRON Biotechnology). Cell viability discovery of cancer‑specific protein markers, which provides assay was performed using MTT assay. The cells were at a the basis for understanding cancer progression, carcinogenesis density of 5x105 cells per well in 24‑well plates and grown and targets of protein molecules for anticancer agents (11). overnight. Subsequently treat the cells were treated with the Herbal products and their components have been identi- indicated concentrations of SCU (0, 25, 50, 75, and 100 µM) fied as exhibiting anticancer effects by targeting dysregulated for 24 h at 37˚C. An amount 50 µl of MTT solution (0.5 mg/ml) genes that contribute to carcinogenesis in several cancer cell was added to each well after 24 h, and incubation was carried lines by multiple cell signaling pathways (12,13). Flavonoids out at 37˚C for 3 h in a dark condition. DMSO (300 µl) was are natural polyphenolic compounds that are abundantly added to each well to solubilize the formazan contained in present in plant parts, especially in leaves and fruits, and the cells, and the absorbance was measured at 540 nm using previous studies have demonstrated several anticancer effects a microplate reader (BioTek Instruments). Cell viability was by regulating multiple cellular mechanisms such as the expressed as a percentage of the control and experiments were PI3K/AKT/mTOR signaling pathway (13,14). Fig. 1A shows conducted in triplicates for each assay condition. Scutellarein (SCU), a flavone, which belongs to the family of flavonoids, that are abundantly present in perpetual herbs, Protein sample preparation for 2‑DE analysis. AGS and such as Scutellaria barbata and Scutellaria baicalensis. SNU484 cells were treated or untreated (control) with SCU Studies have demonstrated that SCU
Load more

Recommended publications
  • Transcriptome Analyses of Rhesus Monkey Pre-Implantation Embryos Reveal A
    Downloaded from genome.cshlp.org on September 23, 2021 - Published by Cold Spring Harbor Laboratory Press Transcriptome analyses of rhesus monkey pre-implantation embryos reveal a reduced capacity for DNA double strand break (DSB) repair in primate oocytes and early embryos Xinyi Wang 1,3,4,5*, Denghui Liu 2,4*, Dajian He 1,3,4,5, Shengbao Suo 2,4, Xian Xia 2,4, Xiechao He1,3,6, Jing-Dong J. Han2#, Ping Zheng1,3,6# Running title: reduced DNA DSB repair in monkey early embryos Affiliations: 1 State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China 2 Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China 3 Yunnan Key Laboratory of Animal Reproduction, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China 4 University of Chinese Academy of Sciences, Beijing, China 5 Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China 6 Primate Research Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China * Xinyi Wang and Denghui Liu contributed equally to this work 1 Downloaded from genome.cshlp.org on September 23, 2021 - Published by Cold Spring Harbor Laboratory Press # Correspondence: Jing-Dong J. Han, Email: [email protected]; Ping Zheng, Email: [email protected] Key words: rhesus monkey, pre-implantation embryo, DNA damage 2 Downloaded from genome.cshlp.org on September 23, 2021 - Published by Cold Spring Harbor Laboratory Press ABSTRACT Pre-implantation embryogenesis encompasses several critical events including genome reprogramming, zygotic genome activation (ZGA) and cell fate commitment.
    [Show full text]
  • Supplemental Table 1. Complete Gene Lists and GO Terms from Figure 3C
    Supplemental Table 1. Complete gene lists and GO terms from Figure 3C. Path 1 Genes: RP11-34P13.15, RP4-758J18.10, VWA1, CHD5, AZIN2, FOXO6, RP11-403I13.8, ARHGAP30, RGS4, LRRN2, RASSF5, SERTAD4, GJC2, RHOU, REEP1, FOXI3, SH3RF3, COL4A4, ZDHHC23, FGFR3, PPP2R2C, CTD-2031P19.4, RNF182, GRM4, PRR15, DGKI, CHMP4C, CALB1, SPAG1, KLF4, ENG, RET, GDF10, ADAMTS14, SPOCK2, MBL1P, ADAM8, LRP4-AS1, CARNS1, DGAT2, CRYAB, AP000783.1, OPCML, PLEKHG6, GDF3, EMP1, RASSF9, FAM101A, STON2, GREM1, ACTC1, CORO2B, FURIN, WFIKKN1, BAIAP3, TMC5, HS3ST4, ZFHX3, NLRP1, RASD1, CACNG4, EMILIN2, L3MBTL4, KLHL14, HMSD, RP11-849I19.1, SALL3, GADD45B, KANK3, CTC- 526N19.1, ZNF888, MMP9, BMP7, PIK3IP1, MCHR1, SYTL5, CAMK2N1, PINK1, ID3, PTPRU, MANEAL, MCOLN3, LRRC8C, NTNG1, KCNC4, RP11, 430C7.5, C1orf95, ID2-AS1, ID2, GDF7, KCNG3, RGPD8, PSD4, CCDC74B, BMPR2, KAT2B, LINC00693, ZNF654, FILIP1L, SH3TC1, CPEB2, NPFFR2, TRPC3, RP11-752L20.3, FAM198B, TLL1, CDH9, PDZD2, CHSY3, GALNT10, FOXQ1, ATXN1, ID4, COL11A2, CNR1, GTF2IP4, FZD1, PAX5, RP11-35N6.1, UNC5B, NKX1-2, FAM196A, EBF3, PRRG4, LRP4, SYT7, PLBD1, GRASP, ALX1, HIP1R, LPAR6, SLITRK6, C16orf89, RP11-491F9.1, MMP2, B3GNT9, NXPH3, TNRC6C-AS1, LDLRAD4, NOL4, SMAD7, HCN2, PDE4A, KANK2, SAMD1, EXOC3L2, IL11, EMILIN3, KCNB1, DOK5, EEF1A2, A4GALT, ADGRG2, ELF4, ABCD1 Term Count % PValue Genes regulation of pathway-restricted GDF3, SMAD7, GDF7, BMPR2, GDF10, GREM1, BMP7, LDLRAD4, SMAD protein phosphorylation 9 6.34 1.31E-08 ENG pathway-restricted SMAD protein GDF3, SMAD7, GDF7, BMPR2, GDF10, GREM1, BMP7, LDLRAD4, phosphorylation
    [Show full text]
  • High-Grade Glioneuronal Tumor with an ARHGEF2–NTRK1 Fusion Gene
    Brain Tumor Pathology (2019) 36:121–128 https://doi.org/10.1007/s10014-019-00345-y CASE REPORT High‑grade glioneuronal tumor with an ARHGEF2–NTRK1 fusion gene Kazuhiko Kurozumi1 · Yoshiko Nakano2 · Joji Ishida1 · Takehiro Tanaka3 · Masatomo Doi4 · Junko Hirato5 · Akihiko Yoshida6 · Kana Washio7 · Akira Shimada7 · Takashi Kohno8 · Koichi Ichimura2 · Hiroyuki Yanai9 · Isao Date1 Received: 1 March 2019 / Accepted: 20 March 2019 / Published online: 22 April 2019 © The Japan Society of Brain Tumor Pathology 2019 Abstract Here, we report a highly unusual case of high-grade glioneuronal tumor with a neurotrophic tropomyosin receptor kinase (NTRK) fusion gene. A 13-year-old girl presented with headache and vomiting and MRI detected two cystic lesions bilaterally in the frontal areas with surrounding edema. The left larger tumor was removed by left frontal craniotomy. The tumor was diagnosed as a high-grade glioneuronal tumor, unclassifed. Methylation profling classifed it as a difuse leptomeningeal glioneuronal tumor (DLGNT) with low confdence. This tumor showed genotypes frequently found in DLGNT such as 1p/19q codeletion without IDH mutation and, however, did not have the typical DLGNT clinical and histological features. RNA sequencing identifed an ARHGEF2 (encoding Rho/Rac guanine nucleotide exchange factor 2)–NTRK1 fusion gene. The presence of recurrent NTRK fusion in glioneuronal tumors has an important implication in the clinical decision making and opens up a possibility of novel targeted therapy. Keywords Pediatric brain tumor · 1p19qLOH · RNA sequencing · NTRK1 Introduction diagnosis of glioneuronal tumors has been sometimes chal- lenging. However, unique molecular signatures have recently Mixed glioneuronal tumors are rare group of brain tumors been identifed, enabling creation of classifcation schemes that consist of glial and neuronal components.
    [Show full text]
  • S41467-020-18249-3.Pdf
    ARTICLE https://doi.org/10.1038/s41467-020-18249-3 OPEN Pharmacologically reversible zonation-dependent endothelial cell transcriptomic changes with neurodegenerative disease associations in the aged brain Lei Zhao1,2,17, Zhongqi Li 1,2,17, Joaquim S. L. Vong2,3,17, Xinyi Chen1,2, Hei-Ming Lai1,2,4,5,6, Leo Y. C. Yan1,2, Junzhe Huang1,2, Samuel K. H. Sy1,2,7, Xiaoyu Tian 8, Yu Huang 8, Ho Yin Edwin Chan5,9, Hon-Cheong So6,8, ✉ ✉ Wai-Lung Ng 10, Yamei Tang11, Wei-Jye Lin12,13, Vincent C. T. Mok1,5,6,14,15 &HoKo 1,2,4,5,6,8,14,16 1234567890():,; The molecular signatures of cells in the brain have been revealed in unprecedented detail, yet the ageing-associated genome-wide expression changes that may contribute to neurovas- cular dysfunction in neurodegenerative diseases remain elusive. Here, we report zonation- dependent transcriptomic changes in aged mouse brain endothelial cells (ECs), which pro- minently implicate altered immune/cytokine signaling in ECs of all vascular segments, and functional changes impacting the blood–brain barrier (BBB) and glucose/energy metabolism especially in capillary ECs (capECs). An overrepresentation of Alzheimer disease (AD) GWAS genes is evident among the human orthologs of the differentially expressed genes of aged capECs, while comparative analysis revealed a subset of concordantly downregulated, functionally important genes in human AD brains. Treatment with exenatide, a glucagon-like peptide-1 receptor agonist, strongly reverses aged mouse brain EC transcriptomic changes and BBB leakage, with associated attenuation of microglial priming. We thus revealed tran- scriptomic alterations underlying brain EC ageing that are complex yet pharmacologically reversible.
    [Show full text]
  • Molecular Effects of Isoflavone Supplementation Human Intervention Studies and Quantitative Models for Risk Assessment
    Molecular effects of isoflavone supplementation Human intervention studies and quantitative models for risk assessment Vera van der Velpen Thesis committee Promotors Prof. Dr Pieter van ‘t Veer Professor of Nutritional Epidemiology Wageningen University Prof. Dr Evert G. Schouten Emeritus Professor of Epidemiology and Prevention Wageningen University Co-promotors Dr Anouk Geelen Assistant professor, Division of Human Nutrition Wageningen University Dr Lydia A. Afman Assistant professor, Division of Human Nutrition Wageningen University Other members Prof. Dr Jaap Keijer, Wageningen University Dr Hubert P.J.M. Noteborn, Netherlands Food en Consumer Product Safety Authority Prof. Dr Yvonne T. van der Schouw, UMC Utrecht Dr Wendy L. Hall, King’s College London This research was conducted under the auspices of the Graduate School VLAG (Advanced studies in Food Technology, Agrobiotechnology, Nutrition and Health Sciences). Molecular effects of isoflavone supplementation Human intervention studies and quantitative models for risk assessment Vera van der Velpen Thesis submitted in fulfilment of the requirements for the degree of doctor at Wageningen University by the authority of the Rector Magnificus Prof. Dr M.J. Kropff, in the presence of the Thesis Committee appointed by the Academic Board to be defended in public on Friday 20 June 2014 at 13.30 p.m. in the Aula. Vera van der Velpen Molecular effects of isoflavone supplementation: Human intervention studies and quantitative models for risk assessment 154 pages PhD thesis, Wageningen University, Wageningen, NL (2014) With references, with summaries in Dutch and English ISBN: 978-94-6173-952-0 ABSTRact Background: Risk assessment can potentially be improved by closely linked experiments in the disciplines of epidemiology and toxicology.
    [Show full text]
  • Pi3kα Inactivation in Leptin Receptor Cells Increases Leptin Sensitivity but Disrupts Growth and Reproduction
    PI3Kα inactivation in leptin receptor cells increases leptin sensitivity but disrupts growth and reproduction David Garcia-Galiano, … , Jennifer W. Hill, Carol F. Elias JCI Insight. 2017;2(23):e96728. https://doi.org/10.1172/jci.insight.96728. Research Article Reproductive biology The role of PI3K in leptin physiology has been difficult to determine due to its actions downstream of several metabolic cues, including insulin. Here, we used a series of mouse models to dissociate the roles of specific PI3K catalytic subunits and of insulin receptor (InsR) downstream of leptin signaling. We show that disruption of p110α and p110β subunits in leptin receptor cells (LRΔα+β) produces a lean phenotype associated with increased energy expenditure, locomotor activity, and thermogenesis. LRΔα+β mice have deficient growth and delayed puberty. Single subunit deletion (i.e., p110α in LRΔα) resulted in similarly increased energy expenditure, deficient growth, and pubertal development, but LRΔα mice have normal locomotor activity and thermogenesis. Blunted PI3K in leptin receptor (LR) cells enhanced leptin sensitivity in metabolic regulation due to increased basal hypothalamic pAKT, leptin-induced pSTAT3, and decreased PTEN levels. However, these mice are unresponsive to leptin’s effects on growth and puberty. We further assessed if these phenotypes were associated with disruption of insulin signaling. LRΔInsR mice have no metabolic or growth deficit and show only mild delay in pubertal completion. Our findings demonstrate that PI3K in LR cells plays an essential role in energy expenditure, growth, and reproduction. These actions are independent from insulin signaling. Find the latest version: https://jci.me/96728/pdf RESEARCH ARTICLE PI3Kα inactivation in leptin receptor cells increases leptin sensitivity but disrupts growth and reproduction David Garcia-Galiano,1 Beatriz C.
    [Show full text]
  • Signature Redacted Thesis Supervisor Certified By
    Single-Cell Transcriptomics of the Mouse Thalamic Reticular Nucleus by Taibo Li S.B., Massachusetts Institute of Technology (2015) Submitted to the Department of Electrical Engineering and Computer Science in partial fulfillment of the requirements for the degree of Master of Engineering in Electrical Engineering and Computer Science at the MASSACHUSETTS INSTITUTE OF TECHNOLOGY June 2017 @ Massachusetts Institute of Technology 2017. All rights reserved. A uthor ... ..................... Department of Electrical Engineering and Computer Science May 25, 2017 Certified by. 3ignature redacted Guoping Feng Poitras Professor of Neuroscience, MIT Signature redacted Thesis Supervisor Certified by... Kasper Lage Assistant Professor, Harvard Medical School Thesis Supervisor Accepted by . Signature redacted Christopher Terman Chairman, Masters of Engineering Thesis Committee MASSACHUSETTS INSTITUTE 0) OF TECHNOLOGY w AUG 14 2017 LIBRARIES 2 Single-Cell Transcriptomics of the Mouse Thalamic Reticular Nucleus by Taibo Li Submitted to the Department of Electrical Engineering and Computer Science on May 25, 2017, in partial fulfillment of the requirements for the degree of Master of Engineering in Electrical Engineering and Computer Science Abstract The thalamic reticular nucleus (TRN) is strategically located at the interface between the cortex and the thalamus, and plays a key role in regulating thalamo-cortical in- teractions. Current understanding of TRN neurobiology has been limited due to the lack of a comprehensive survey of TRN heterogeneity. In this thesis, I developed an integrative computational framework to analyze the single-nucleus RNA sequencing data of mouse TRN in a data-driven manner. By combining transcriptomic, genetic, and functional proteomic data, I discovered novel insights into the molecular mecha- nisms through which TRN regulates sensory gating, and suggested targeted follow-up experiments to validate these findings.
    [Show full text]
  • A Chromosome Level Genome of Astyanax Mexicanus Surface Fish for Comparing Population
    bioRxiv preprint doi: https://doi.org/10.1101/2020.07.06.189654; this version posted July 6, 2020. 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. 1 Title 2 A chromosome level genome of Astyanax mexicanus surface fish for comparing population- 3 specific genetic differences contributing to trait evolution. 4 5 Authors 6 Wesley C. Warren1, Tyler E. Boggs2, Richard Borowsky3, Brian M. Carlson4, Estephany 7 Ferrufino5, Joshua B. Gross2, LaDeana Hillier6, Zhilian Hu7, Alex C. Keene8, Alexander Kenzior9, 8 Johanna E. Kowalko5, Chad Tomlinson10, Milinn Kremitzki10, Madeleine E. Lemieux11, Tina 9 Graves-Lindsay10, Suzanne E. McGaugh12, Jeff T. Miller12, Mathilda Mommersteeg7, Rachel L. 10 Moran12, Robert Peuß9, Edward Rice1, Misty R. Riddle13, Itzel Sifuentes-Romero5, Bethany A. 11 Stanhope5,8, Clifford J. Tabin13, Sunishka Thakur5, Yamamoto Yoshiyuki14, Nicolas Rohner9,15 12 13 Authors for correspondence: Wesley C. Warren ([email protected]), Nicolas Rohner 14 ([email protected]) 15 16 Affiliation 17 1Department of Animal Sciences, Department of Surgery, Institute for Data Science and 18 Informatics, University of Missouri, Bond Life Sciences Center, Columbia, MO 19 2 Department of Biological Sciences, University of Cincinnati, Cincinnati, OH 20 3 Department of Biology, New York University, New York, NY 21 4 Department of Biology, The College of Wooster, Wooster, OH 22 5 Harriet L. Wilkes Honors College, Florida Atlantic University, Jupiter FL 23 6 Department of Genome Sciences, University of Washington, Seattle, WA 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.07.06.189654; this version posted July 6, 2020.
    [Show full text]
  • The Genetics of Bipolar Disorder
    Molecular Psychiatry (2008) 13, 742–771 & 2008 Nature Publishing Group All rights reserved 1359-4184/08 $30.00 www.nature.com/mp FEATURE REVIEW The genetics of bipolar disorder: genome ‘hot regions,’ genes, new potential candidates and future directions A Serretti and L Mandelli Institute of Psychiatry, University of Bologna, Bologna, Italy Bipolar disorder (BP) is a complex disorder caused by a number of liability genes interacting with the environment. In recent years, a large number of linkage and association studies have been conducted producing an extremely large number of findings often not replicated or partially replicated. Further, results from linkage and association studies are not always easily comparable. Unfortunately, at present a comprehensive coverage of available evidence is still lacking. In the present paper, we summarized results obtained from both linkage and association studies in BP. Further, we indicated new potential interesting genes, located in genome ‘hot regions’ for BP and being expressed in the brain. We reviewed published studies on the subject till December 2007. We precisely localized regions where positive linkage has been found, by the NCBI Map viewer (http://www.ncbi.nlm.nih.gov/mapview/); further, we identified genes located in interesting areas and expressed in the brain, by the Entrez gene, Unigene databases (http://www.ncbi.nlm.nih.gov/entrez/) and Human Protein Reference Database (http://www.hprd.org); these genes could be of interest in future investigations. The review of association studies gave interesting results, as a number of genes seem to be definitively involved in BP, such as SLC6A4, TPH2, DRD4, SLC6A3, DAOA, DTNBP1, NRG1, DISC1 and BDNF.
    [Show full text]
  • RNA-Seq-Based Analysis of Cortisol-Induced Differential Gene
    animals Article RNA-Seq-Based Analysis of Cortisol-Induced Differential Gene Expression Associated with Piscirickettsia salmonis Infection in Rainbow Trout (Oncorhynchus mykiss) Myotubes Rodrigo Zuloaga 1,2, Phillip Dettleff 1 , Macarena Bastias-Molina 3, Claudio Meneses 3, Claudia Altamirano 4, Juan Antonio Valdés 1,2,5 and Alfredo Molina 1,2,5,* 1 Laboratorio de Biotecnología Molecular, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370186, Chile; [email protected] (R.Z.); [email protected] (P.D.); [email protected] (J.A.V.) 2 Interdisciplinary Center for Aquaculture Research (INCAR), Concepción 4030000, Chile 3 Centro de Biotecnología Vegetal, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370186, Chile; [email protected] (M.B.-M.); [email protected] (C.M.) 4 Laboratorio de Cultivos Celulares, Escuela de Ingeniería Bioquímica, Pontificia Universidad Católica de Valparaíso, Valparaíso 2362803, Chile; [email protected] 5 Centro de Investigación Marina Quintay (CIMARQ), Facultad de Ciencias de la Vida, Universidad Andres Bello, Valparaíso 2340000, Chile * Correspondence: [email protected]; Tel.: +56-227703067 Simple Summary: Skeletal muscle is the most abundant tissue in fish and the main product of the Citation: Zuloaga, R.; Dettleff, P.; Chilean salmonid aquaculture industry. Intensive farming conditions generate stress and increased Bastias-Molina, M.; Meneses, C.; susceptibility to infectious diseases, such as salmonid rickettsial septicemia (SRS), that
    [Show full text]
  • ADHD) Gene Networks in Children of Both African American and European American Ancestry
    G C A T T A C G G C A T genes Article Rare Recurrent Variants in Noncoding Regions Impact Attention-Deficit Hyperactivity Disorder (ADHD) Gene Networks in Children of both African American and European American Ancestry Yichuan Liu 1 , Xiao Chang 1, Hui-Qi Qu 1 , Lifeng Tian 1 , Joseph Glessner 1, Jingchun Qu 1, Dong Li 1, Haijun Qiu 1, Patrick Sleiman 1,2 and Hakon Hakonarson 1,2,3,* 1 Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA; [email protected] (Y.L.); [email protected] (X.C.); [email protected] (H.-Q.Q.); [email protected] (L.T.); [email protected] (J.G.); [email protected] (J.Q.); [email protected] (D.L.); [email protected] (H.Q.); [email protected] (P.S.) 2 Division of Human Genetics, Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA 3 Department of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA * Correspondence: [email protected]; Tel.: +1-267-426-0088 Abstract: Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with poorly understood molecular mechanisms that results in significant impairment in children. In this study, we sought to assess the role of rare recurrent variants in non-European populations and outside of coding regions. We generated whole genome sequence (WGS) data on 875 individuals, Citation: Liu, Y.; Chang, X.; Qu, including 205 ADHD cases and 670 non-ADHD controls. The cases included 116 African Americans H.-Q.; Tian, L.; Glessner, J.; Qu, J.; Li, (AA) and 89 European Americans (EA), and the controls included 408 AA and 262 EA.
    [Show full text]
  • Differential Expression Profile Prioritization of Positional Candidate Glaucoma Genes the GLC1C Locus
    LABORATORY SCIENCES Differential Expression Profile Prioritization of Positional Candidate Glaucoma Genes The GLC1C Locus Frank W. Rozsa, PhD; Kathleen M. Scott, BS; Hemant Pawar, PhD; John R. Samples, MD; Mary K. Wirtz, PhD; Julia E. Richards, PhD Objectives: To develop and apply a model for priori- est because of moderate expression and changes in tization of candidate glaucoma genes. expression. Transcription factor ZBTB38 emerges as an interesting candidate gene because of the overall expres- Methods: This Affymetrix GeneChip (Affymetrix, Santa sion level, differential expression, and function. Clara, Calif) study of gene expression in primary cul- ture human trabecular meshwork cells uses a positional Conclusions: Only1geneintheGLC1C interval fits our differential expression profile model for prioritization of model for differential expression under multiple glau- candidate genes within the GLC1C genetic inclusion in- coma risk conditions. The use of multiple prioritization terval. models resulted in filtering 7 candidate genes of higher interest out of the 41 known genes in the region. Results: Sixteen genes were expressed under all condi- tions within the GLC1C interval. TMEM22 was the only Clinical Relevance: This study identified a small sub- gene within the interval with differential expression in set of genes that are most likely to harbor mutations that the same direction under both conditions tested. Two cause glaucoma linked to GLC1C. genes, ATP1B3 and COPB2, are of interest in the con- text of a protein-misfolding model for candidate selec- tion. SLC25A36, PCCB, and FNDC6 are of lesser inter- Arch Ophthalmol. 2007;125:117-127 IGH PREVALENCE AND PO- identification of additional GLC1C fami- tential for severe out- lies7,18-20 who provide optimal samples for come combine to make screening candidate genes for muta- adult-onset primary tions.7,18,20 The existence of 2 distinct open-angle glaucoma GLC1C haplotypes suggests that muta- (POAG) a significant public health prob- tions will not be limited to rare descen- H1 lem.
    [Show full text]