{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T07:12:39Z","timestamp":1777533159767,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.pntd.0011727","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T00:00:00Z","timestamp":1700611200000}}],"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T00:00:00Z","timestamp":1699574400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["No. 2021YFC2300800, 2021YFC2300804"],"award-info":[{"award-number":["No. 2021YFC2300800, 2021YFC2300804"]}]},{"name":"Nursery key Fund of Henan Cancer Hospital"},{"name":"Training Program for Young scholars in Universities of Henan Province","award":["2021GGJS084"],"award-info":[{"award-number":["2021GGJS084"]}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2018A0303 13750"],"award-info":[{"award-number":["2018A0303 13750"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Clonorchiasis, caused by the infection of <jats:italic>Clonorchis sinensis<\/jats:italic> (<jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic>), is a kind of neglected tropical disease, but it is highly related to cholangiocarcinoma. It has been well known that NO from chronic inflammation responses are thought to be a major component of the damage and ultimate carcinogenesis ESPs such as nitric oxide synthase interacting protein (NOSIP) are thought to enhance the damage. The objective of this study was to identify the protein candidates interact with recombinant <jats:italic>Cs<\/jats:italic>NOSIP (r<jats:italic>Cs<\/jats:italic>NOSIP) and explore their role involved in CCA development or progression.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We applied HuProt microarray containing 21,000 probe sets for a systematic identification of r<jats:italic>Cs<\/jats:italic>NOSIP-binding proteins and grouped binding hits by gene function. Pull-down assays were used to confirm the interaction of r<jats:italic>Cs<\/jats:italic>NOSIP with alveolar soft part sarcoma (ASPSCR-1) and sirtuins 5 (Sirt-5). ASPSCR-1\/Sirt-5 over-expression and siRNA knockdown experiments were employed for obtain of ASPSCR-1\/Sirt-5 high or low expression (ASP-oe\/Sirt5-oe or ASP-si\/Sirt5-si) cholangiocarcinoma cell line (CCLP-1) cells. Nitric oxide (NO) and reactive oxygen species assay (ROS) as well as cell proliferation and wound-healing assays were performed to observe the effect of r<jats:italic>Cs<\/jats:italic>NOSIP on ASP-oe\/Sirt5-oe or ASP-si\/Sirt5-si CCLP-1 cells.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Seventy candidate proteins protein \"hits\" were detected as r<jats:italic>Cs<\/jats:italic>NOSIP-binding proteins by HuProt microarray and bioinformatics analysis. Pull down assay showed that ASPSCR-1 and Sirt-5 could interact with r<jats:italic>Cs<\/jats:italic>NOSIP. In addition, endotoxin-free-r<jats:italic>Cs<\/jats:italic>NOSIP could increase the production of NO and ROS and promote the migration of CCLP-1 cells, while its effect on enhancing cell proliferation was not significant. Furthermore, ROS\/NO production, proliferation, or migration were increased in ASP-si or Sirt5-si CCLP-1 cells but decreased in Asp-oe or Sirt5-oe CCLP-1 cells when stimulated with r<jats:italic>Cs<\/jats:italic>NOSIP.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Our findings suggest that <jats:italic>Cs<\/jats:italic>NOSIP as a component of <jats:italic>Cs<\/jats:italic>ESPs might promote the development and invasion of CCA and Sirt5\/ ASPSCR1 as host molecules might play a novel protective role against adverse stimulus during <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> infection. This work supports the idea that <jats:italic>Cs<\/jats:italic>ESPs induce the occurrence and progression of CCA through ROS\/RNS-induced oxidative and nitrative DNA damage.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0011727","type":"journal-article","created":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T18:36:52Z","timestamp":1699641412000},"page":"e0011727","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["ASPSCR-1 and Sirt-5 alleviate Clonorchis liver fluke rCsNOSIP-induced oxidative stress, proliferation, and migration in cholangiocarcinoma cells"],"prefix":"10.1371","volume":"17","author":[{"given":"Meng","family":"Bian","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanzong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijun","family":"Bi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Tingjin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinbing","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9578-6784","authenticated-orcid":true,"given":"Qingxia","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,11,10]]},"reference":[{"key":"pntd.0011727.ref001","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S1473-3099(04)01252-6","article-title":"Clonorchiasis: a key foodborne zoonosis","volume":"5","author":"ZR Lun","year":"2005","journal-title":"China. Lancet Infect Dis"},{"key":"pntd.0011727.ref002","doi-asserted-by":"crossref","first-page":"e0008287","DOI":"10.1371\/journal.pntd.0008287","article-title":"Amino acids serve as an important energy source for adult flukes of Clonorchis sinensis","volume":"14","author":"S Li","year":"2020","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0011727.ref003","doi-asserted-by":"crossref","first-page":"e2606","DOI":"10.1371\/journal.pntd.0002606","article-title":"Molecular characterization of severin from Clonorchis sinensis excretory\/secretory products and its potential anti-apoptotic role in hepatocarcinoma PLC cells.","volume":"7","author":"X Chen","year":"2013","journal-title":"PloS Negl Trop Dis"},{"key":"pntd.0011727.ref004","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.biotechadv.2010.07.006","article-title":"Progress on the transcriptomics of carcinogenic liver flukes of humans\u2013unique biological and biotechnological prospects","volume":"28","author":"ND Young","year":"2010","journal-title":"Biotechnol Adv"},{"key":"pntd.0011727.ref005","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1111\/j.1349-7006.2009.01458.x","article-title":"Epidemiology of cholangiocarcinoma: an update focusing on risk factors","volume":"101","author":"HR Shin","year":"2010","journal-title":"Cancer Sci"},{"key":"pntd.0011727.ref006","doi-asserted-by":"crossref","first-page":"93","DOI":"10.4269\/ajtmh.2006.75.93","article-title":"Clonorchis sinensis infection and increasing risk of cholangiocarcinoma in the Republic of Korea","volume":"75","author":"MK Lim","year":"2006","journal-title":"Am J Trop Med Hyg"},{"key":"pntd.0011727.ref007","doi-asserted-by":"crossref","first-page":"e0003641","DOI":"10.1371\/journal.pntd.0003641","article-title":"Advanced enzymology, expression profile and immune response of Clonorchis sinensis hexokinase show its application potential for prevention and control of clonorchiasis.","volume":"9","author":"T Chen","year":"2015","journal-title":"PloS Negl Trop Dis"},{"key":"pntd.0011727.ref008","doi-asserted-by":"crossref","first-page":"e201","DOI":"10.1371\/journal.pmed.0040201","article-title":"Liver fluke induces cholangiocarcinoma","volume":"4","author":"B Sripa","year":"2007","journal-title":"PloS Med"},{"key":"pntd.0011727.ref009","article-title":"Csseverin inhibits apoptosis through mitochondria-mediated pathways triggered by Ca2 + dyshomeostasis in hepatocarcinoma PLC cells.","volume":"11","author":"M Shi","year":"2017","journal-title":"PloS Negl Trop Dis."},{"key":"pntd.0011727.ref010","first-page":"38","article-title":"Nitrative and oxidative DNA damage in infection-related carcinogenesis in relation to cancer stem cells","volume":"1","author":"S Kawanishi","year":"2017","journal-title":"Genes Environ"},{"issue":"5\u20136","key":"pntd.0011727.ref011","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1089\/ars.2006.8.1047","article-title":"Oxidative and nitrative DNA damage as biomarker for carcinogenesis with special reference to inflammation","volume":"8","author":"S Kawanishi","year":"2006","journal-title":"Antioxid Redox Signal"},{"key":"pntd.0011727.ref012","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.ijpara.2011.11.001","article-title":"Free radicals enzymatically triggered by Clonorchis sinensis excretory-secretory products cause NF-kB-mediated inflammation in human cholangiocarcinoma cells","volume":"42","author":"JH Nam","year":"2012","journal-title":"Int J Parasitol"},{"key":"pntd.0011727.ref013","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/bph.14533","article-title":"Nitric oxide synthase enzymology in the 20 years after the Nobel Prize","volume":"176","author":"DJ Stuehr","year":"2019","journal-title":"Br J Pharmacol"},{"key":"pntd.0011727.ref014","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1186\/cc2353","article-title":"Bench-to-bedside review: microvascular dysfunction in sepsis\u2014hemodynamics, oxygen transport, and nitric oxide","volume":"7","author":"RM Bateman","year":"2003","journal-title":"Crit Care"},{"key":"pntd.0011727.ref015","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1369\/jhc.4A6453.2005","article-title":"NOSIP and its interacting protein, eNOS, in the rat trachea and lung. Journal of Histochemistry &","volume":"53","author":"P K\u00f6nig","year":"2005","journal-title":"Cytochemistry"},{"key":"pntd.0011727.ref016","doi-asserted-by":"crossref","first-page":"119018","DOI":"10.1016\/j.bbamcr.2021.119018","article-title":"nNOS induction and NOSIP interaction impact granulopoiesis and neutrophil differentiation by modulating nitric oxide generation","volume":"186","author":"S Sadaf","year":"2021","journal-title":"Biochim Biophys Acta Mol Cell Res"},{"key":"pntd.0011727.ref017","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1007\/s00436-014-3820-1","article-title":"Identification, immunolocalization, and immunological characterization of nitric oxide synthase-interacting protein from Clonorchis sinensis","volume":"113","author":"M Bian","year":"2014","journal-title":"Parasitol Res"},{"key":"pntd.0011727.ref018","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1038\/s41467-019-08902-x","article-title":"ABHD5 blunts the sensitivity of colorectal cancer to fluorouracil via promoting autophagic uracil yield","volume":"10","author":"J Ou","year":"2019","journal-title":"Nat Commun"},{"key":"pntd.0011727.ref019","doi-asserted-by":"crossref","first-page":"637871","DOI":"10.3389\/fonc.2021.637871","article-title":"Identification of Novel Autoantibodies Based on the Human Proteomic Chips and Evaluation of Their Performance in the Detection of Gastric Cancer.","volume":"11","author":"C Cui","year":"2021","journal-title":"Front Oncol"},{"issue":"1\u20132","key":"pntd.0011727.ref020","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/s11010-011-1189-3","article-title":"Gene\/protein expression level, immunolocalization and binding characteristics of fatty acid binding protein from Clonorchis sinensis (CsFABP).","volume":"363","author":"L Huang","year":"2012","journal-title":"Mol Cell Biochem"},{"key":"pntd.0011727.ref021","doi-asserted-by":"crossref","first-page":"295","DOI":"10.3390\/ijms21010295","article-title":"Granulosa-Lutein Cell Sirtuin Gene Expression Profiles Differ between Normal Donors and Infertile Women","volume":"21","author":"R Gonz\u00e1lez-Fern\u00e1ndez","year":"2019","journal-title":"Int J Mol Sci"},{"key":"pntd.0011727.ref022","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in real-time RT-PCR","volume":"29","author":"MW Pfaffl","year":"2001","journal-title":"Nucleic Acids Res"},{"key":"pntd.0011727.ref023","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1186\/s13071-015-1248-9","article-title":"Identification and characterization of Clonorchis sinensis cathepsin B proteases in the pathogenesis of clonorchiasis.","volume":"8","author":"W Chen","year":"2015","journal-title":"Parasit Vectors."},{"key":"pntd.0011727.ref024","doi-asserted-by":"crossref","first-page":"236","DOI":"10.5009\/gnl17102","article-title":"Liver Fluke-Associated Biliary Tract Cancer.","volume":"12","author":"P Prueksapanich","year":"2018","journal-title":"Gut Liver"},{"key":"pntd.0011727.ref025","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s00436-015-4723-5","article-title":"Investigation on oxidative stress of nitric oxide synthase interacting protein from Clonorchis sinensis","volume":"115","author":"M Bian","year":"2016","journal-title":"Parasitol Res"},{"key":"pntd.0011727.ref026","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1007\/s00436-008-1283-y","article-title":"Resistance of cholangiocarcinoma cells to parthenolide-induced apoptosis by the excretory-secretory products of Clonorchis sinensis","volume":"104","author":"YJ Kim","year":"2009","journal-title":"Parasitol Res"},{"key":"pntd.0011727.ref027","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s00436-007-0778-2","article-title":"Proliferative effects of excretory\/secretory products from Clonorchis sinensis on the human epithelial cell line HEK293 via regulation of the transcription factor E2F1","volume":"102","author":"YJ Kim","year":"2008","journal-title":"Parasitol Res"},{"key":"pntd.0011727.ref028","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1186\/s13071-017-2179-4","article-title":"Clonorchis sinensis granulin: identification, immunolocalization, and function in promoting the metastasis of cholangiocarcinoma and hepatocellular carcinoma.","volume":"10","author":"C Wang","year":"2017","journal-title":"Parasit Vectors"},{"key":"pntd.0011727.ref029","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.cbpc.2019.05.013","article-title":"NO\/cGMP\/PKG activation protects Drosophila cells subjected to hypoxic stress","volume":"223","author":"O Mahneva","year":"2019","journal-title":"Comp Biochem Physiol C Toxicol Pharmacol"},{"key":"pntd.0011727.ref030","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1089\/ars.2017.7290","article-title":"The Role of Sirtuins in Antioxidant and Redox Signaling","volume":"28","author":"CK Singh","year":"2018","journal-title":"Antioxid Redox Signal"},{"key":"pntd.0011727.ref031","doi-asserted-by":"crossref","first-page":"H1375","DOI":"10.1152\/ajpheart.00053.2015","article-title":"The role of sirtuins in cardiac disease","volume":"309","author":"S Matsushima","year":"2015","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"pntd.0011727.ref032","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.bbrc.2013.10.033","article-title":"SIRT5 desuccinylates and activates SOD1 to eliminate ROS","volume":"441","author":"ZF Lin","year":"2013","journal-title":"Biochem Biophys Res Commun"},{"key":"pntd.0011727.ref033","doi-asserted-by":"crossref","first-page":"e45124","DOI":"10.15252\/embr.201745124","article-title":"SIRT5 inhibits peroxisomal ACOX1 to prevent oxidative damage and is downregulated in liver cancer","volume":"19","author":"XF Chen","year":"2018","journal-title":"EMBO Rep"},{"key":"pntd.0011727.ref034","doi-asserted-by":"crossref","first-page":"590","DOI":"10.5483\/BMBRep.2016.49.11.109","article-title":"Clonorchis sinensis, an oriental liver fluke, as a human biological agent of cholangiocarcinoma: a brief review.","volume":"49","author":"TS Kim","year":"2016","journal-title":"BMB Rep"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0011727","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T00:00:00Z","timestamp":1700611200000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0011727","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T18:43:24Z","timestamp":1700678604000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0011727"}},"subtitle":[],"editor":[{"given":"Krystyna","family":"Cwiklinski","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2023,11,10]]},"references-count":34,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,11,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0011727","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pntd.0011727","asserted-by":"object"}]},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,10]]}}}