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Screening and Identification of Key Biomarkers in Clear Cell Renal Cell Carcinoma Based on Bioinformatics Analysis
bioRxiv preprint doi: https://doi.org/10.1101/2020.12.21.423889; this version posted December 23, 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 The copyright holder for this preprint (which was not certified by peer review) is the author/funder.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. Screening and identification of key biomarkers in clear cell renal cell carcinoma based on bioinformatics analysis Basavaraj Vastrad1, Chanabasayya Vastrad*2 , Iranna Kotturshetti 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. 3. Department of Ayurveda, Rajiv Gandhi Education Society`s Ayurvedic Medical College, Ron, Karnataka 562209, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India bioRxiv preprint doi: https://doi.org/10.1101/2020.12.21.423889; this version posted December 23, 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 The copyright holder for this preprint (which was not certified by peer review) is the author/funder.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. Abstract Clear cell renal cell carcinoma (ccRCC) is one of the most common types of malignancy of the urinary system. The pathogenesis and effective diagnosis of ccRCC have become popular topics for research in the previous decade. In the current study, an integrated bioinformatics analysis was performed to identify core genes associated in ccRCC. An expression dataset (GSE105261) was downloaded from the Gene Expression Omnibus database, and included 26 ccRCC and 9 normal kideny samples. Assessment of the microarray dataset led to the recognition of differentially expressed genes (DEGs), which was subsequently used for pathway and gene ontology (GO) enrichment analysis. -
Upregulation of Peroxisome Proliferator-Activated Receptor-Α And
Upregulation of peroxisome proliferator-activated receptor-α and the lipid metabolism pathway promotes carcinogenesis of ampullary cancer Chih-Yang Wang, Ying-Jui Chao, Yi-Ling Chen, Tzu-Wen Wang, Nam Nhut Phan, Hui-Ping Hsu, Yan-Shen Shan, Ming-Derg Lai 1 Supplementary Table 1. Demographics and clinical outcomes of five patients with ampullary cancer Time of Tumor Time to Age Differentia survival/ Sex Staging size Morphology Recurrence recurrence Condition (years) tion expired (cm) (months) (months) T2N0, 51 F 211 Polypoid Unknown No -- Survived 193 stage Ib T2N0, 2.41.5 58 F Mixed Good Yes 14 Expired 17 stage Ib 0.6 T3N0, 4.53.5 68 M Polypoid Good No -- Survived 162 stage IIA 1.2 T3N0, 66 M 110.8 Ulcerative Good Yes 64 Expired 227 stage IIA T3N0, 60 M 21.81 Mixed Moderate Yes 5.6 Expired 16.7 stage IIA 2 Supplementary Table 2. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of an ampullary cancer microarray using the Database for Annotation, Visualization and Integrated Discovery (DAVID). This table contains only pathways with p values that ranged 0.0001~0.05. KEGG Pathway p value Genes Pentose and 1.50E-04 UGT1A6, CRYL1, UGT1A8, AKR1B1, UGT2B11, UGT2A3, glucuronate UGT2B10, UGT2B7, XYLB interconversions Drug metabolism 1.63E-04 CYP3A4, XDH, UGT1A6, CYP3A5, CES2, CYP3A7, UGT1A8, NAT2, UGT2B11, DPYD, UGT2A3, UGT2B10, UGT2B7 Maturity-onset 2.43E-04 HNF1A, HNF4A, SLC2A2, PKLR, NEUROD1, HNF4G, diabetes of the PDX1, NR5A2, NKX2-2 young Starch and sucrose 6.03E-04 GBA3, UGT1A6, G6PC, UGT1A8, ENPP3, MGAM, SI, metabolism -
Small-Molecule Inhibition of 6-Phosphofructo-2-Kinase Activity Suppresses Glycolytic Flux and Tumor Growth
110 Small-molecule inhibition of 6-phosphofructo-2-kinase activity suppresses glycolytic flux and tumor growth Brian Clem,1,3 Sucheta Telang,1,3 Amy Clem,1,3 reduces the intracellular concentration of Fru-2,6-BP, Abdullah Yalcin,1,2,3 Jason Meier,2 glucose uptake, and growth of established tumors in vivo. Alan Simmons,1,3 Mary Ann Rasku,1,3 Taken together, these data support the clinical development Sengodagounder Arumugam,1,3 of 3PO and other PFKFB3 inhibitors as chemotherapeutic William L. Dean,2,3 John Eaton,1,3 Andrew Lane,1,3 agents. [Mol Cancer Ther 2008;7(1):110–20] John O. Trent,1,2,3 and Jason Chesney1,2,3 Departments of 1Medicine and 2Biochemistry and Molecular Introduction Biology and 3Molecular Targets Group, James Graham Brown Neoplastic transformation causes a marked increase in Cancer Center, University of Louisville, Louisville, Kentucky glucose uptake and catabolic conversion to lactate, which forms the basis for the most specific cancer diagnostic 18 Abstract examination—positron emission tomography of 2- F- fluoro-2-deoxyglucose (18F-2-DG) uptake (1). The protein 6-Phosphofructo-1-kinase, a rate-limiting enzyme of products of several oncogenes directly increase glycolytic glycolysis, is activated in neoplastic cells by fructose-2,6- flux even under normoxic conditions, a phenomenon bisphosphate (Fru-2,6-BP), a product of four 6-phospho- originally termed the Warburg effect (2, 3). For example, fructo-2-kinase/fructose-2,6-bisphosphatase isozymes c-myc is a transcription factor that promotes the expression (PFKFB1-4). The inducible PFKFB3 isozyme is constitu- of glycolytic enzyme mRNAs, and its expression is increased tively expressed by neoplastic cells and required for the in several human cancers regardless of the oxygen pressure high glycolytic rate and anchorage-independent growth of (4, 5). -
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Published OnlineFirst February 12, 2018; DOI: 10.1158/0008-5472.CAN-17-2215 Cancer Metabolism and Chemical Biology Research RSK Regulates PFK-2 Activity to Promote Metabolic Rewiring in Melanoma Thibault Houles1, Simon-Pierre Gravel2,Genevieve Lavoie1, Sejeong Shin3, Mathilde Savall1, Antoine Meant 1, Benoit Grondin1, Louis Gaboury1,4, Sang-Oh Yoon3, Julie St-Pierre2, and Philippe P. Roux1,4 Abstract Metabolic reprogramming is a hallmark of cancer that includes glycolytic flux in melanoma cells, suggesting an important role for increased glucose uptake and accelerated aerobic glycolysis. This RSK in BRAF-mediated metabolic rewiring. Consistent with this, phenotypeisrequiredtofulfill anabolic demands associated with expression of a phosphorylation-deficient mutant of PFKFB2 aberrant cell proliferation and is often mediated by oncogenic decreased aerobic glycolysis and reduced the growth of melanoma drivers such as activated BRAF. In this study, we show that the in mice. Together, these results indicate that RSK-mediated phos- MAPK-activated p90 ribosomal S6 kinase (RSK) is necessary to phorylation of PFKFB2 plays a key role in the metabolism and maintain glycolytic metabolism in BRAF-mutated melanoma growth of BRAF-mutated melanomas. cells. RSK directly phosphorylated the regulatory domain of Significance: RSK promotes glycolytic metabolism and the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2), growth of BRAF-mutated melanoma by driving phosphory- an enzyme that catalyzes the synthesis of fructose-2,6-bisphosphate lation of an important glycolytic enzyme. Cancer Res; 78(9); during glycolysis. Inhibition of RSK reduced PFKFB2 activity and 2191–204. Ó2018 AACR. Introduction but recently developed therapies that target components of the MAPK pathway have demonstrated survival advantage in pati- Melanoma is the most aggressive form of skin cancer and arises ents with BRAF-mutated tumors (7). -
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. -
UCP1-Independent Thermogenesis in Brown/Beige Adipocytes: Classical Creatine Kinase/Phosphocreatine Shuttle Instead of “Futile Creatine Cycling”
UCP1-independent thermogenesis in brown/beige adipocytes: classical creatine kinase/phosphocreatine shuttle instead of “futile creatine cycling”. Theo Wallimann1*), Malgorzata Tokarska-Schlattner2) Laurence Kay2) and Uwe Schlattner2,3*) 1) Biology Dept. ETH-Zurich, Switzerland, emeritus, E-mail address: [email protected] 2) University Grenoble Alpes and Inserm U1055, Laboratory of Fundamental and Applied Bioenergetics & SFR Environmental and Systems Biology, Grenoble, France, E-mail address: [email protected] 3) Institut Universitaire de France (IUF), Paris, France *) joint corresponding authors Abstract Various studies have identified creatine kinase (CK) and creatine (Cr) as important players for thermogenesis. More recently, they have been specifically linked to UCP1-independent thermogenesis in beige/brown adipocytes, and a “Cr-driven futile cycle” within mitochondria was proposed as the mechanistic basis. Here, we provide a critical appraisal of such a mechanism, which would require a rather undefined phosphocreatine phosphatase. As alternative explanation, we suggest instead that the well-known functions of the CK system, that is ATP buffering and shuttling of high-energy phosphocreatine (PCr) from sites of ATP generation to sites of ATP utilization, are also working in brown/beige adipocytes. There, the CK/PCr system would be shunted between ATP generation, at the mitochondria and/or glycolysis, and ATP hydrolysis at the ER/SR. This would largely facilitate high-throughput calcium pumping by the ATP-dependent Ca2+ pump (SERCA) as described also in skeletal and cardiac muscle. This very CK/PCr system would then support adipocyte SERCA2b function and, in tandem with adipocyte ryanodine receptor (RyR2) and/or inositol 1,4,5- 2+ triphosphate receptor (IP3-R3), facilitate thermogenic futile Ca cycling that has been described to operate in UCP1-independent, but ATP-dependent non-shivering thermogenesis. -
Multivariate Meta-Analysis of Differential Principal Components Underlying Human Primed and Naive-Like Pluripotent States
bioRxiv preprint doi: https://doi.org/10.1101/2020.10.20.347666; this version posted October 21, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. October 20, 2020 To: bioRxiv Multivariate Meta-Analysis of Differential Principal Components underlying Human Primed and Naive-like Pluripotent States Kory R. Johnson1*, Barbara S. Mallon2, Yang C. Fann1, and Kevin G. Chen2*, 1Intramural IT and Bioinformatics Program, 2NIH Stem Cell Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA Keywords: human pluripotent stem cells; naive pluripotency, meta-analysis, principal component analysis, t-SNE, consensus clustering *Correspondence to: Dr. Kory R. Johnson ([email protected]) Dr. Kevin G. Chen ([email protected]) 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.10.20.347666; this version posted October 21, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. ABSTRACT The ground or naive pluripotent state of human pluripotent stem cells (hPSCs), which was initially established in mouse embryonic stem cells (mESCs), is an emerging and tentative concept. To verify this important concept in hPSCs, we performed a multivariate meta-analysis of major hPSC datasets via the combined analytic powers of percentile normalization, principal component analysis (PCA), t-distributed stochastic neighbor embedding (t-SNE), and SC3 consensus clustering. -
Understanding the Central Role of Citrate in the Metabolism of Cancer Cells and Tumors: an Update
International Journal of Molecular Sciences Review Understanding the Central Role of Citrate in the Metabolism of Cancer Cells and Tumors: An Update Philippe Icard 1,2,3,*, Antoine Coquerel 1,4, Zherui Wu 5 , Joseph Gligorov 6, David Fuks 7, Ludovic Fournel 3,8, Hubert Lincet 9,10 and Luca Simula 11 1 Medical School, Université Caen Normandie, CHU de Caen, 14000 Caen, France; [email protected] 2 UNICAEN, INSERM U1086 Interdisciplinary Research Unit for Cancer Prevention and Treatment, Normandie Université, 14000 Caen, France 3 Service de Chirurgie Thoracique, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, APHP, Paris-Descartes University, 75014 Paris, France; [email protected] 4 INSERM U1075, COMETE Mobilités: Attention, Orientation, Chronobiologie, Université Caen, 14000 Caen, France 5 School of Medicine, Shenzhen University, Shenzhen 518000, China; [email protected] 6 Oncology Department, Tenon Hospital, Pierre et Marie Curie University, 75020 Paris, France; [email protected] 7 Service de Chirurgie Digestive et Hépato-Biliaire, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, APHP, Paris-Descartes University, 75014 Paris, France; [email protected] 8 Descartes Faculty of Medicine, University of Paris, Paris Center, 75006 Paris, France 9 INSERM U1052, CNRS UMR5286, Cancer Research Center of Lyon (CRCL), 69008 Lyon, France; [email protected] 10 ISPB, Faculté de Pharmacie, Université Lyon 1, 69373 Lyon, France 11 Department of Infection, Immunity and Inflammation, Institut Cochin, INSERM U1016, CNRS UMR8104, Citation: Icard, P.; Coquerel, A.; Wu, University of Paris, 75014 Paris, France; [email protected] Z.; Gligorov, J.; Fuks, D.; Fournel, L.; * Correspondence: [email protected] Lincet, H.; Simula, L. -
Oncorequisite Role of an Aldehyde Dehydrogenase in the Pathogenesis of T-Cell Acute Lymphoblastic Leukemia
Acute Lymphoblastic Leukemia SUPPLEMENTARY APPENDIX Oncorequisite role of an aldehyde dehydrogenase in the pathogenesis of T-cell acute lymphoblastic leukemia Chujing Zhang, 1 Stella Amanda, 1 Cheng Wang, 2 Tze King Tan, 1 Muhammad Zulfaqar Ali, 1 Wei Zhong Leong, 1 Ley Moy Ng, 1 Shojiro Kitajima, 3 Zhenhua Li, 4 Allen Eng Juh Yeoh, 1,4 Shi Hao Tan 1 and Takaomi Sanda 1,5 1Cancer Science Institute of Singapore, National University of Singapore, Singapore; 2Department of Anatomy, National University of Singapore, Singapore; 3Institute for Advanced Biosciences, Keio University, Tsuruoka, Japan; 4VIVA-NUS CenTRAL, Department of Pedi - atrics, National University of Singapore, Singapore and 5Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. ©2021 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol. 2019.245639 Received: December 18, 2019. Accepted: May 14, 2020. Pre-published: May 15, 2020. Correspondence: TAKAOMI SANDA - [email protected] Zhang et al Roles of ALDH in T-ALL Supplementary Information Supplementary Materials and Methods Cell culture and reagents All human leukemia cell lines were cultured in RPMI-1640 medium (BioWest) supplemented with 10% FBS (BioWest). 293T cells were maintained in DMEM medium (BioWest) supplemented with 10% FBS and penicillin/streptomycin (Life Technologies). All-trans retinaldehyde was purchased from Sigma-Aldrich. Glucose free and Glutamine free RPMI- 1640 media were purchased from ThermoFisher. Patient derived xenograft (PDX) sample T-ALL patient-derived PDX sample (DFCI15) was kindly provided by Alejandro Gutierrez (Boston Children’s Hospital, Boston). Mouse studies were conducted according to the recommendations from the Institutional Animal Care and Use Committee (IACUC) and all protocols were approved by the Committee at the National University of Singapore (NUS). -
GRIN3A and MAPT Stimulate Nerve Overgrowth in Macrodactyly
MOLECULAR MEDICINE REPORTS 14: 5637-5643, 2016 GRIN3A and MAPT stimulate nerve overgrowth in macrodactyly XU SHI1*, LU LU2*, XIU JIN3, BIN LIU4, XIGUANG SUN4, LAIJIN LU4 and YANFANG JIANG1,5 1Department of Genetic Diagnosis Center, Central Laboratory; Departments of 2Breast Surgery, 3Burn Surgery and 4Hand and Foot Surgery, The First Hospital of Jilin University, Changchun, Jilin 130000; 5Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun, Jilin 130000, P.R. China Received September 30, 2015; Accepted October 12, 2016 DOI: 10.3892/mmr.2016.5923 Abstract. As an uncommon and congenital condition, to abnormal nerve proliferation and underpin the pathogenesis macrodactyly is characterized by an increase in the size of all of macrodactyly, and provide potential application targets in the elements or structures of the digits or toes; however, the nerve tissue regeneration engineering. underlying pathogenesis remains to be fully elucidated. In the present study, the gene expression profiles of abnormal nerves Introduction were examined in three patients with macrodactyly using microarray analysis to identify potential genes contributing Macrodactyly is an uncommon congenital condition character- to nerve overgrowth. Gene expression profiling in the nerve ized by an increase in the size of all the elements or structures tissue samples were scanned using the microarray and the of the digits or toes, including phalanges, tendons, vessels, differentially expressed genes were verified at the transcrip- subcutaneous fat and finger nails. The malformation often tion level using reverse transcription-quantitative polymerase occurs unilaterally or asymmetrically and affects more than chain reaction analysis. Western blot analysis was used to one digit or toe. -
Identification of Potential Key Genes and Pathway Linked with Sporadic Creutzfeldt-Jakob Disease Based on Integrated Bioinformatics Analyses
medRxiv preprint doi: https://doi.org/10.1101/2020.12.21.20248688; this version posted December 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Identification of potential key genes and pathway linked with sporadic Creutzfeldt-Jakob disease based on integrated bioinformatics analyses Basavaraj Vastrad1, Chanabasayya Vastrad*2 , Iranna Kotturshetti 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. 3. Department of Ayurveda, Rajiv Gandhi Education Society`s Ayurvedic Medical College, Ron, Karnataka 562209, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2020.12.21.20248688; this version posted December 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Abstract Sporadic Creutzfeldt-Jakob disease (sCJD) is neurodegenerative disease also called prion disease linked with poor prognosis. The aim of the current study was to illuminate the underlying molecular mechanisms of sCJD. The mRNA microarray dataset GSE124571 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened. -
Emerging Roles of P53 Family Members in Glucose Metabolism
International Journal of Molecular Sciences Review Emerging Roles of p53 Family Members in Glucose Metabolism Yoko Itahana and Koji Itahana * Cancer and Stem Cell Biology Program, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore; [email protected] * Correspondence: [email protected]; Tel.: +65-6516-2554; Fax: +65-6221-2402 Received: 19 January 2018; Accepted: 22 February 2018; Published: 8 March 2018 Abstract: Glucose is the key source for most organisms to provide energy, as well as the key source for metabolites to generate building blocks in cells. The deregulation of glucose homeostasis occurs in various diseases, including the enhanced aerobic glycolysis that is observed in cancers, and insulin resistance in diabetes. Although p53 is thought to suppress tumorigenesis primarily by inducing cell cycle arrest, apoptosis, and senescence in response to stress, the non-canonical functions of p53 in cellular energy homeostasis and metabolism are also emerging as critical factors for tumor suppression. Increasing evidence suggests that p53 plays a significant role in regulating glucose homeostasis. Furthermore, the p53 family members p63 and p73, as well as gain-of-function p53 mutants, are also involved in glucose metabolism. Indeed, how this protein family regulates cellular energy levels is complicated and difficult to disentangle. This review discusses the roles of the p53 family in multiple metabolic processes, such as glycolysis, gluconeogenesis, aerobic respiration, and autophagy. We also discuss how the dysregulation of the p53 family in these processes leads to diseases such as cancer and diabetes. Elucidating the complexities of the p53 family members in glucose homeostasis will improve our understanding of these diseases.