DOCSLIB.ORG

Bothrops Jararaca Snake Venom Modulates Key Cancer-Related Proteins in Breast Tumor Cell Lines

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Bothrops Jararaca Snake Venom Modulates Key Cancer-Related Proteins in Breast Tumor Cell Lines toxins Article Bothrops Jararaca Snake Venom Modulates Key Cancer-Related Proteins in Breast Tumor Cell Lines Carolina Yukiko Kisaki 1, Stephanie Santos Suehiro Arcos 1, Fabio Montoni 1, Wellington da Silva Santos 1, Hamida Macêdo Calacina 1, Ismael Feitosa Lima 1, Daniela Cajado-Carvalho 1 , Emer Suavinho Ferro 2 , Milton Yutaka Nishiyama-Jr 1,* and Leo Kei Iwai 1,* 1 Laboratory of Applied Toxinology (LETA) and Center of Toxins, Immune-Response and Cell Signaling (CeTICS), Butantan Institute, São Paulo 05503-900, Brazil; [email protected] (C.Y.K.); [email protected] (S.S.S.A.); [email protected] (F.M.); [email protected] (W.d.S.S.); [email protected] (H.M.C.); [email protected] (I.F.L.); [email protected] (D.C.-C.) 2 Department of Pharmacology, Biomedical Sciences Institute (ICB), University of São Paulo (USP), São Paulo 05508-000, Brazil; [email protected] * Correspondence: [email protected] (M.Y.N.-J.); [email protected] (L.K.I.) Abstract: Cancer is characterized by the development of abnormal cells that divide in an uncontrolled way and may spread into other tissues where they may infiltrate and destroy normal body tissue. Several previous reports have described biochemical anti-tumorigenic properties of crude snake venom or its components, including their capability of inhibiting cell proliferation and promoting cell death. However, to the best of our knowledge, there is no work describing cancer cell pro- teomic changes following treatment with snake venoms. In this work we describe the quantitative changes in proteomics of MCF7 and MDA-MB-231 breast tumor cell lines following treatment with Citation: Kisaki, C.Y.; Arcos, S.S.S.; Bothrops jararaca snake venom, as well as the functional implications of the proteomic changes. Cell Montoni, F.; da Silva Santos, W.; lines were treated with sub-toxic doses at either 0.63 µg/mL (low) or 2.5 µg/mL (high) of B. jararaca Calacina, H.M.; Lima, I.F.; venom for 24 h, conditions that cause no cell death per se. Proteomics analysis was conducted Cajado-Carvalho, D.; Ferro, E.S.; on a nano-scale liquid chromatography coupled on-line with mass spectrometry (nLC-MS/MS). Nishiyama-Jr, M.Y.; Iwai, L.K. More than 1000 proteins were identified and evaluated from each cell line treated with either the Bothrops Jararaca Snake Venom low or high dose of the snake venom. Protein profiling upon venom treatment showed differential Modulates Key Cancer-Related Proteins in Breast Tumor Cell Lines. expression of several proteins related to cancer cell metabolism, immune response, and inflammation. Toxins 2021, 13, 519. https://doi.org/ Among the identified proteins we highlight histone H3, SNX3, HEL-S-156an, MTCH2, RPS, MCC2, 10.3390/toxins13080519 IGF2BP1, and GSTM3. These data suggest that sub-toxic doses of B. jararaca venom have potential to modulate cancer-development related protein targets in cancer cells. This work illustrates a novel Received: 5 July 2021 biochemical strategy to identify therapeutic targets against cancer cell growth and survival. Accepted: 19 July 2021 Published: 25 July 2021 Keywords: mass spectrometry; proteome; snake venom; Bothrops jararaca; breast cancer Publisher’s Note: MDPI stays neutral Key Contribution: We describe that B. jararaca snake venom modulates specific protein pathways with regard to jurisdictional claims in related to cancer cell growth and invasion, which could be a useful approach to identify novel published maps and institutional affil- therapeutic targets for cancer treatment. iations. 1. Introduction Copyright: © 2021 by the authors. Ophidian accidents constitute a serious public health problem in Brazil, with an av- Licensee MDPI, Basel, Switzerland. erage of 29,000 cases and 125 deaths reported every year (Brazilian Ministry of Health, This article is an open access article 2019) [1]. Approximately 80% of ophidian accidents are caused by snakes of the Viperidae distributed under the terms and family, more specifically of the Bothrops genus [2]. Among them, about 25% lead to death conditions of the Creative Commons or sequels capable of generating temporary or permanent incapacity for work and custom- Attribution (CC BY) license (https:// ary activities. Venom from the Bothrops jararaca (B. jararaca) snake is a complex mixture creativecommons.org/licenses/by/ 4.0/). composed of proteins, peptides, amino acids, nucleotides, lipids, and carbohydrates that Toxins 2021, 13, 519. https://doi.org/10.3390/toxins13080519 https://www.mdpi.com/journal/toxins Toxins 2021, 13, 519 2 of 28 present a range of different actions when they are isolated or together [3–7], leading to hemotoxic, cardiotoxic, cytotoxic, or neurotoxic effects [8,9]. Several previous reports have defined the proteomics composition of Bothrops venoms [5,10–16]. These studies have shown that Bothrops venoms are composed of various classes of toxin, including metalloproteinases, serine proteinases, phospholipases A2, and C-type lectins, the most abundant components participating in the local and systemic envenomation effects. The venom of B. jararaca engenders three main activities: proteolytic, coagulant, and hemolytic. The proteolytic activity causes degradation of extracellular matrix proteins, plasma, and cell surface [17], which represents an important factor for the clinical charac- terization of a bothropic accident [2,18]. In addition, venom can cause local tissue lesion, myonecrosis, edema, cardiovascular alterations, hypovolemic shock, coagulation alteration and renal alterations, resulting from the combined action of the enzymatic and toxic ac- tivity of the venom [19]. About 90 to 95% of the dry weight of the B. jararaca venom is composed of a complex mixture of proteins, mainly metalloproteinases, serine proteinases, phospholipases (PLA2), and L-amino acid oxidases. The metalloproteinases comprise most of the venom composition [20,21]. They are proteolytic enzymes associated with fibrinolysis and coagulation, and they are involved in cell migration and tissue repair, besides being related to pathological effects such as cancer [22,23]. In terms of therapeutic interventions, protease inhibitors have been shown to inhibit homeostasis and thrombosis by acting on the coagulation cascade [24]. The third major component of the venom, PLA2, is an enzyme capable of hydrolyzing the ester bonds at the sn2 position of glycerolphos- pholipids, releasing arachidonic acid, important for the biosynthesis of many mediators involved in inflammation, such as prostaglandins, thromboxanes, and leukotrienes [25]. Finally, the L-amino acid oxidases (LAAOs), which make up about 1 to 9% of the venom composition [26], are flavoenzymes belonging to the class of oxidoreductases, which pro- duce alpha-keto acid, hydrogen peroxide, and ammonia [27,28]. However, when there is a high production of hydrogen peroxide, it has been found that L-amino acid oxidases can induce apoptosis in mammalian endothelial cells [29]. Snake venom constituents have been isolated and studied for their therapeutic poten- tial in the treatment of various diseases. One example is Eptifibatide, marketed as Integrilin, derived from the Echis carinatus snake venom and produced by Millennium Pharmaceu- ticals and Schering-Plow. It is used as an antiplatelet drug [30]. Another example is the angiotensin I converting enzyme inhibitor Captopril produced by Bristol-Myers Squibb whose active component was derived from B. jararaca venom. It is used for the treatment against hypertension and renal insufficiency [31,32]. In addition to the potential use of the derivatives of snake venom toxins in the treatment of non-malignant diseases [33], several studies have described anti-tumorigenic characteristics of snake venom, stating that snake venom may be capable of inhibiting cell proliferation and promoting cell death by different means: inducing apoptosis in cancer cells by increasing the influx of Ca2+, inducing the release of cytochrome C, decreasing or increasing the expression of proteins that control the cell cycle, and causing damage to cell membranes [26,34–36]. With the goal of searching novel therapy against cancer, studies have characterized the proteins, peptides or enzymes derived from snake venom to identify components that are capable of interfering with the transport of substances or signal transduction across the membrane or disrupting the cell membrane [35,37]. With the rapid advances of nano-scale liquid chromatography (nLC) and mass spec- trometry (MS) technologies in the last two decades, nLC-MS/MS-based proteomics analysis has been widely applied as a powerful tool for biomarker discovery to improve cancer therapy [38,39]. A number of studies have characterized the biochemical and physiological action of venom or isolated venom derivatives on cell lines or tissues [40–43]. In addition, several works have shown proteomic changes of cancer cell lines upon drug treatment that suggest molecular mechanisms of drug action, including diverse effects on proteasome regulation, metabolic processes, and oxidative stress [44,45]. Toxins 2021, 13, x FOR PEER REVIEW 3 of 28 43]. In addition, several works have shown proteomic changes of cancer cell lines upon Toxins 2021, 13, 519 drug treatment that suggest molecular mechanisms of drug action, including diverse3 of 28 effects on proteasome regulation, metabolic processes, and oxidative stress [44,45]. However, to the best of our knowledge, there has been no report that describes the effects of B. jararaca snake venom treatment on breast cancer-related cell proteome. In the However, to the best of our knowledge, there has been no report that describes the present study, nLC-MS/MS was used to characterize the effects of sub-toxic doses of B. effects of B. jararaca snake venom treatment on breast cancer-related cell proteome. In jararaca snake venom on two different breast cancer cell lines MCF7 and MDA-MB-231. the present study, nLC-MS/MS was used to characterize the effects of sub-toxic doses of MCF7 and MDA-MB-231 are non-metastatic and metastatic tumor cell lines, respectively. B. jararaca snake venom on two different breast cancer cell lines MCF7 and MDA-MB-231.
Load more

Recommended publications
  • Phylogenetic Diversity, Habitat Loss and Conservation in South
    Diversity and Distributions, (Diversity Distrib.) (2014) 20, 1108–1119 BIODIVERSITY Phylogenetic diversity, habitat loss and RESEARCH conservation in South American pitvipers (Crotalinae: Bothrops and Bothrocophias) Jessica Fenker1, Leonardo G. Tedeschi1, Robert Alexander Pyron2 and Cristiano de C. Nogueira1*,† 1Departamento de Zoologia, Universidade de ABSTRACT Brasılia, 70910-9004 Brasılia, Distrito Aim To analyze impacts of habitat loss on evolutionary diversity and to test Federal, Brazil, 2Department of Biological widely used biodiversity metrics as surrogates for phylogenetic diversity, we Sciences, The George Washington University, 2023 G. St. NW, Washington, DC 20052, study spatial and taxonomic patterns of phylogenetic diversity in a wide-rang- USA ing endemic Neotropical snake lineage. Location South America and the Antilles. Methods We updated distribution maps for 41 taxa, using species distribution A Journal of Conservation Biogeography models and a revised presence-records database. We estimated evolutionary dis- tinctiveness (ED) for each taxon using recent molecular and morphological phylogenies and weighted these values with two measures of extinction risk: percentages of habitat loss and IUCN threat status. We mapped phylogenetic diversity and richness levels and compared phylogenetic distances in pitviper subsets selected via endemism, richness, threat, habitat loss, biome type and the presence in biodiversity hotspots to values obtained in randomized assemblages. Results Evolutionary distinctiveness differed according to the phylogeny used, and conservation assessment ranks varied according to the chosen proxy of extinction risk. Two of the three main areas of high phylogenetic diversity were coincident with areas of high species richness. A third area was identified only by one phylogeny and was not a richness hotspot. Faunal assemblages identified by level of endemism, habitat loss, biome type or the presence in biodiversity hotspots captured phylogenetic diversity levels no better than random assem- blages.
    [Show full text]
  • Transcription-Factor Polymorphism Associated with Tissue-Specific Gene
    bioRxiv preprint doi: https://doi.org/10.1101/405936; this version posted August 31, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. TF-TWAS: Transcription-factor polymorphism associated with tissue-specific gene expression Yi-Ching Tang 1, Assaf Gottlieb 1* 1 Center for precision health, School of Biomedical informatics, University of Texas Health Science Center at Houston, Houston, TX, 77030 * Corresponding author: Assaf Gottlieb, Center for Precision Health, School of Biomedical Informatics, University of Texas Health Science Center in Houston, 7000 Fannin st, Houston, TX, 77030 Email: [email protected] Tel: +1-(713) 5003698 Running Title: TF-TWAS: TF polymorphism affecting gene expression Keywords: “transcriptome-wide association studies”, “TWAS”, “Transcription Factor polymorphism” bioRxiv preprint doi: https://doi.org/10.1101/405936; this version posted August 31, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Abstract Transcriptional regulation is associated with a broad range of diseases. Methods associating genetic polymorphism with gene transcription levels offer key insights for understanding the transcriptional regulation plan. The majority of gene imputation methods focus on modeling polymorphism in the cis regions of the gene, partially owing to the large genetic search space. We hypothesize that polymorphism within transcription factors (TFs) may help explain transcription levels of their transcribed genes.
    [Show full text]
  • De Los Reptiles Del Yasuní
    guía dinámica de los reptiles del yasuní omar torres coordinador editorial Lista de especies Número de especies: 113 Amphisbaenia Amphisbaenidae Amphisbaena bassleri, Culebras ciegas Squamata: Serpentes Boidae Boa constrictor, Boas matacaballo Corallus hortulanus, Boas de los jardines Epicrates cenchria, Boas arcoiris Eunectes murinus, Anacondas Colubridae: Dipsadinae Atractus major, Culebras tierreras cafés Atractus collaris, Culebras tierreras de collares Atractus elaps, Falsas corales tierreras Atractus occipitoalbus, Culebras tierreras grises Atractus snethlageae, Culebras tierreras Clelia clelia, Chontas Dipsas catesbyi, Culebras caracoleras de Catesby Dipsas indica, Culebras caracoleras neotropicales Drepanoides anomalus, Culebras hoz Erythrolamprus reginae, Culebras terrestres reales Erythrolamprus typhlus, Culebras terrestres ciegas Erythrolamprus guentheri, Falsas corales de nuca rosa Helicops angulatus, Culebras de agua anguladas Helicops pastazae, Culebras de agua de Pastaza Helicops leopardinus, Culebras de agua leopardo Helicops petersi, Culebras de agua de Peters Hydrops triangularis, Culebras de agua triángulo Hydrops martii, Culebras de agua amazónicas Imantodes lentiferus, Cordoncillos del Amazonas Imantodes cenchoa, Cordoncillos comunes Leptodeira annulata, Serpientes ojos de gato anilladas Oxyrhopus petolarius, Falsas corales amazónicas Oxyrhopus melanogenys, Falsas corales oscuras Oxyrhopus vanidicus, Falsas corales Philodryas argentea, Serpientes liana verdes de banda plateada Philodryas viridissima, Serpientes corredoras
    [Show full text]
  • The Modular Nature of Bradykinin-Potentiating Peptides
    Sciani and Pimenta Journal of Venomous Animals and Toxins including Tropical Diseases (2017) 23:45 DOI 10.1186/s40409-017-0134-7 REVIEW Open Access The modular nature of bradykinin- potentiating peptides isolated from snake venoms Juliana Mozer Sciani and Daniel Carvalho Pimenta* Abstract Bradykinin-potentiating peptides (BPPs) are molecules discovered by Sergio Ferreira – who found them in the venom of Bothrops jararaca in the 1960s – that literally potentiate the action of bradykinin in vivo by, allegedly, inhibiting the angiotensin-converting enzymes. After administration, the global physiological effect of BPP is the decrease of the blood pressure. Due to this interesting effect, one of these peptides was used by David Cushman and Miguel Ondetti to develop a hypotensive drug, the widely known captopril, vastly employed on hypertension treatment. From that time on, many studies on BPPs have been conducted, basically describing new peptides and assaying their pharmacological effects, mostly in comparison to captopryl. After compiling most of these data, we are proposing that snake BPPs are ‘modular’ peptidic molecules, in which the combination of given amino acid ‘blocks’ results in the different existing peptides (BPPs), commonly found in snake venom. We have observed that there would be mandatory modules (present in all snake BPPs), such as the N-terminal pyroglutamic acid and C-terminal QIPP, and optional modules (amino acid blocks present in some of them), such as AP or WAQ. Scattered between these modules, there might be other amino acids that would ‘complete’ the peptide, without disrupting the signature of the classical BPP. This modular arrangement would represent an important evolutionary advantage in terms of biological diversity that might have its origins either at the genomic or at the post-translational modification levels.
    [Show full text]
  • Relationship of Venom Ontogeny and Diet in Bothrops
    Herpetologica. 55(2), 1999, 200-204 @ 1999 hy The Herpetologists' League, Inc. RELATIONSHIP OF VENOM ONTOGENY AND DIET IN BOTHROPS DENIS V ANDRADE AND AUGUSTO S. ABE Departamento de Zoologia, Universidade Estadual Paulista, c. p. 199, 13506-900, Rio Claro, São Paulo, Brazil ABSTRACT: We studied ontogenetic changes in venom toxicity of the pitvipers Bothrops jararaca and B. altematus in order to evaluate the relationship between venom action and diet. Toxicity tests (LD",,) were performed for the venoms of adult and juvenile snakes on mice and bullfrog froglets, which represented endothermic and ectothermic prey respectively. The venom of juveniles of B. jararaca, but not of B. altematus, had a higher toxicity on anurans than that of adults. This finding is consistent with the feeding habits of these two species, because juveniles of B. jararaca feed mainly on small anurans and lizards, shifting to endothermic prey at maturity, whereas B. altematus preys mainly on endotherms throughout its life. Venom toxicity in endotherms was higher for adults of B. jararaca compared to juveniles, a feature not observed for B. altematus. It is proposed that prey death!immobilization is the main function of the venom of juvenile snakes. As the snake grows, the digestive role of venom may become increasingly important, because adults prey upon large and bulky prey. The importance of adult venoms in prey digestion is reflected in their higher proteolytic activity. Key words: Bothrops; Electrophoresis; Venom ontogeny; Venom specificity; Viperidae SNAKESare strictly camivorous and al- that ontogenetic variation could be related ways ingest their prey whole, and for many to differences between the feeding habits species feeding episodes occur sporadical- of juvenile and adult snakes (Gans and EI- ly on relatively large animals (Greene, liot, 1968; Sazima, 1991).
    [Show full text]
  • DF6216-CSRP1 Antibody
    Affinity Biosciences website:www.affbiotech.com order:[email protected] CSRP1 Antibody Cat.#: DF6216 Concn.: 1mg/ml Mol.Wt.: 21kDa Size: 50ul,100ul,200ul Source: Rabbit Clonality: Polyclonal Application: WB 1:500-1:2000, IHC 1:50-1:200, ELISA(peptide) 1:20000-1:40000 *The optimal dilutions should be determined by the end user. Reactivity: Human,Mouse,Rat Purification: The antiserum was purified by peptide affinity chromatography using SulfoLink™ Coupling Resin (Thermo Fisher Scientific). Specificity: CSRP1 Antibody detects endogenous levels of total CSRP1. Immunogen: A synthesized peptide derived from human CSRP1, corresponding to a region within the internal amino acids. Uniprot: P21291 Description: This gene encodes a member of the cysteine-rich protein (CSRP) family. This gene family includes a group of LIM domain proteins, which may be involved in regulatory processes important for development and cellular differentiation. The LIM/double zinc-finger motif found in this gene product occurs in proteins with critical functions in gene regulation, cell growth, and somatic differentiation. Alternatively spliced transcript variants have been described. [provided by RefSeq, Aug 2010] Storage Condition and Rabbit IgG in phosphate buffered saline , pH 7.4, 150mM Buffer: NaCl, 0.02% sodium azide and 50% glycerol.Store at -20 °C.Stable for 12 months from date of receipt. Western blot analysis of CSRP1 expression in Mouse lung lysate 1 / 2 Affinity Biosciences website:www.affbiotech.com order:[email protected] DF6216 at 1/100 staining Mouse brain tissue by IHC-P. The sample was formaldehyde fixed and a heat mediated antigen retrieval step in citrate buffer was performed.
    [Show full text]
  • Histone H3.3 Maintains Genome Integrity During Mammalian Development
    Downloaded from genesdev.cshlp.org on September 25, 2021 - Published by Cold Spring Harbor Laboratory Press Histone H3.3 maintains genome integrity during mammalian development Chuan-Wei Jang, Yoichiro Shibata, Joshua Starmer, Della Yee, and Terry Magnuson Department of Genetics, Carolina Center for Genome Sciences, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599-7264, USA Histone H3.3 is a highly conserved histone H3 replacement variant in metazoans and has been implicated in many important biological processes, including cell differentiation and reprogramming. Germline and somatic mutations in H3.3 genomic incorporation pathway components or in H3.3 encoding genes have been associated with human congenital diseases and cancers, respectively. However, the role of H3.3 in mammalian development remains un- clear. To address this question, we generated H3.3-null mouse models through classical genetic approaches. We found that H3.3 plays an essential role in mouse development. Complete depletion of H3.3 leads to developmental retardation and early embryonic lethality. At the cellular level, H3.3 loss triggers cell cycle suppression and cell death. Surprisingly, H3.3 depletion does not dramatically disrupt gene regulation in the developing embryo. Instead, H3.3 depletion causes dysfunction of heterochromatin structures at telomeres, centromeres, and pericentromeric regions of chromosomes, leading to mitotic defects. The resulting karyotypical abnormalities and DNA damage lead to p53 pathway activation. In summary, our results reveal that an important function of H3.3 is to support chro- mosomal heterochromatic structures, thus maintaining genome integrity during mammalian development. [Keywords: histone H3.3; genome integrity; transcriptional regulation; cell proliferation; apoptosis; mouse embryonic development] Supplemental material is available for this article.
    [Show full text]
  • Essential Genes and Their Role in Autism Spectrum Disorder
    University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2017 Essential Genes And Their Role In Autism Spectrum Disorder Xiao Ji University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Bioinformatics Commons, and the Genetics Commons Recommended Citation Ji, Xiao, "Essential Genes And Their Role In Autism Spectrum Disorder" (2017). Publicly Accessible Penn Dissertations. 2369. https://repository.upenn.edu/edissertations/2369 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/2369 For more information, please contact [email protected]. Essential Genes And Their Role In Autism Spectrum Disorder Abstract Essential genes (EGs) play central roles in fundamental cellular processes and are required for the survival of an organism. EGs are enriched for human disease genes and are under strong purifying selection. This intolerance to deleterious mutations, commonly observed haploinsufficiency and the importance of EGs in pre- and postnatal development suggests a possible cumulative effect of deleterious variants in EGs on complex neurodevelopmental disorders. Autism spectrum disorder (ASD) is a heterogeneous, highly heritable neurodevelopmental syndrome characterized by impaired social interaction, communication and repetitive behavior. More and more genetic evidence points to a polygenic model of ASD and it is estimated that hundreds of genes contribute to ASD. The central question addressed in this dissertation is whether genes with a strong effect on survival and fitness (i.e. EGs) play a specific oler in ASD risk. I compiled a comprehensive catalog of 3,915 mammalian EGs by combining human orthologs of lethal genes in knockout mice and genes responsible for cell-based essentiality.
    [Show full text]
  • Screening and Identification of Hub Genes in Bladder Cancer by Bioinformatics Analysis and KIF11 Is a Potential Prognostic Biomarker
    ONCOLOGY LETTERS 21: 205, 2021 Screening and identification of hub genes in bladder cancer by bioinformatics analysis and KIF11 is a potential prognostic biomarker XIAO‑CONG MO1,2*, ZI‑TONG ZHANG1,3*, MENG‑JIA SONG1,2, ZI‑QI ZHOU1,2, JIAN‑XIONG ZENG1,2, YU‑FEI DU1,2, FENG‑ZE SUN1,2, JIE‑YING YANG1,2, JUN‑YI HE1,2, YUE HUANG1,2, JIAN‑CHUAN XIA1,2 and DE‑SHENG WENG1,2 1State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine; 2Department of Biotherapy, Sun Yat‑Sen University Cancer Center; 3Department of Radiation Oncology, Sun Yat‑Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China Received July 31, 2020; Accepted December 18, 2020 DOI: 10.3892/ol.2021.12466 Abstract. Bladder cancer (BC) is the ninth most common immunohistochemistry and western blotting. In summary, lethal malignancy worldwide. Great efforts have been devoted KIF11 was significantly upregulated in BC and might act as to clarify the pathogenesis of BC, but the underlying molecular a potential prognostic biomarker. The present identification mechanisms remain unclear. To screen for the genes associated of DEGs and hub genes in BC may provide novel insight for with the progression and carcinogenesis of BC, three datasets investigating the molecular mechanisms of BC. were obtained from the Gene Expression Omnibus. A total of 37 tumor and 16 non‑cancerous samples were analyzed to Introduction identify differentially expressed genes (DEGs). Subsequently, 141 genes were identified, including 55 upregulated and Bladder cancer (BC) is the ninth most common malignancy 86 downregulated genes. The protein‑protein interaction worldwide with substantial morbidity and mortality.
    [Show full text]
  • Inhibition of SNW1 Association with Spliceosomal Proteins Promotes
    Cancer Medicine Open Access ORIGINAL RESEARCH Inhibition of SNW1 association with spliceosomal proteins promotes apoptosis in breast cancer cells Naoki Sato1, Masao Maeda2, Mai Sugiyama2, Satoko Ito2, Toshinori Hyodo2, Akio Masuda3, Nobuyuki Tsunoda1, Toshio Kokuryo1, Michinari Hamaguchi2, Masato Nagino1 & Takeshi Senga2 1Department of Surgical Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550, Japan 2Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550, Japan 3Division of Neurogenetics, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550, Japan Keywords Abstract Apoptosis, EFTUD2, PRPF8, RNA splicing, SNRNP200, SNW1 RNA splicing is a fundamental process for protein synthesis. Recent studies have reported that drugs that inhibit splicing have cytotoxic effects on various Correspondence tumor cell lines. In this report, we demonstrate that depletion of SNW1, a Takeshi Senga, 65 Tsurumai, Showa, Nagoya component of the spliceosome, induces apoptosis in breast cancer cells. Proteo- 466-8550, Japan. Tel: 81-52-744-2463; mics and biochemical analyses revealed that SNW1 directly associates with Fax: 81-52-744-2464; other spliceosome components, including EFTUD2 (Snu114) and SNRNP200 E-mail: [email protected] (Brr2). The SKIP region of SNW1 interacted with the N-terminus of EFTUD2 Funding Information as well as two independent regions in the C-terminus of SNRNP200. Similar to This research was funded by a grant from SNW1 depletion, knockdown of EFTUD2 increased the numbers of apoptotic the Ministry of Education, Culture, Sports, cells. Furthermore, we demonstrate that exogenous expression of either the Science and Technology of Japan SKIP region of SNW1 or the N-terminus region of EFTUD2 significantly pro- (Nanomedicine molecular science, 23107010.
    [Show full text]
  • Venomics of Trimeresurus (Popeia) Nebularis, the Cameron Highlands Pit Viper from Malaysia: Insights Into Venom Proteome, Toxicity and Neutralization of Antivenom
    toxins Article Venomics of Trimeresurus (Popeia) nebularis, the Cameron Highlands Pit Viper from Malaysia: Insights into Venom Proteome, Toxicity and Neutralization of Antivenom Choo Hock Tan 1,*, Kae Yi Tan 2 , Tzu Shan Ng 2, Evan S.H. Quah 3 , Ahmad Khaldun Ismail 4 , Sumana Khomvilai 5, Visith Sitprija 5 and Nget Hong Tan 2 1 Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia; 2 Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia; [email protected] (K.Y.T.); [email protected] (T.S.N.); [email protected] (N.H.T.) 3 School of Biological Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia; [email protected] 4 Department of Emergency Medicine, Universiti Kebangsaan Malaysia Medical Centre, 56000 Kuala Lumpur, Malaysia; [email protected] 5 Thai Red Cross Society, Queen Saovabha Memorial Institute, Bangkok 10330, Thailand; [email protected] (S.K.); [email protected] (V.S.) * Correspondence: [email protected] Received: 31 December 2018; Accepted: 30 January 2019; Published: 6 February 2019 Abstract: Trimeresurus nebularis is a montane pit viper that causes bites and envenomation to various communities in the central highland region of Malaysia, in particular Cameron’s Highlands. To unravel the venom composition of this species, the venom proteins were digested by trypsin and subjected to nano-liquid chromatography-tandem mass spectrometry (LC-MS/MS) for proteomic profiling. Snake venom metalloproteinases (SVMP) dominated the venom proteome by 48.42% of total venom proteins, with a characteristic distribution of P-III: P-II classes in a ratio of 2:1, while P-I class was undetected.
    [Show full text]
  • Systemic Surfaceome Profiling Identifies Target Antigens for Immune-Based Therapy in Subtypes of Advanced Prostate Cancer
    Systemic surfaceome profiling identifies target antigens for immune-based therapy in subtypes of advanced prostate cancer John K. Leea,b,c, Nathanael J. Bangayand, Timothy Chaie, Bryan A. Smithf, Tiffany E. Parivaf, Sangwon Yung, Ajay Vashishth, Qingfu Zhangi,j, Jung Wook Parkf, Eva Coreyk, Jiaoti Huangi, Thomas G. Graeberc,d,l,m, James Wohlschlegelh, and Owen N. Wittec,d,f,n,o,1 aDivision of Hematology and Oncology, Department of Medicine, University of California, Los Angeles, CA 90095; bInstitute of Urologic Oncology, Department of Urology, University of California, Los Angeles, CA 90095; cJonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095; dDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; eStanford University School of Medicine, Palo Alto, CA 94305; fDepartment of Microbiology, Immunology, and Medical Genetics, University of California, Los Angeles, CA 90095; gYale School of Medicine, New Haven, CT 06510; hDepartment of Biological Chemistry, University of California, Los Angeles, CA 90095; iDepartment of Pathology, Duke University School of Medicine, Durham, NC 27708; jDepartment of Pathology, China Medical University, 110001 Shenyang, People’s Republic of China; kDepartment of Urology, University of Washington School of Medicine, Seattle, WA 98195; lCrump Institute for Molecular Imaging, University of California, Los Angeles, CA 90095; mUCLA Metabolomics Center, University of California, Los Angeles, CA 900095; nParker Institute for Cancer Immunotherapy,
    [Show full text]