{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T07:41:13Z","timestamp":1770277273756,"version":"3.49.0"},"posted":{"date-parts":[[2023,5,22]]},"group-title":"Microbiology","reference-count":72,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,5,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Chronic infection with\n                  <jats:italic>O. viverrini<\/jats:italic>\n                  has been linked to the development of cholangiocarcinoma (CCA), which is a major public health burden in the Lower Mekong River Basin countries, including Thailand, Lao PDR, Vietnam and Cambodia. Despite its importance, the exact mechanisms by which\n                  <jats:italic>O. viverrini<\/jats:italic>\n                  promotes CCA are largely unknown. In this study, we characterized different extracellular vesicle populations released by\n                  <jats:italic>O. viverrini<\/jats:italic>\n                  (\n                  <jats:italic>Ov<\/jats:italic>\n                  EVs) using proteomic and transcriptomic analyses and investigated their potential role in host-parasite interactions. While 120k\n                  <jats:italic>Ov<\/jats:italic>\n                  EVs promoted cell proliferation in H69 cells at different concentrations, 15k\n                  <jats:italic>Ov<\/jats:italic>\n                  EVs did not produce any effect compared to controls. The proteomic analysis of both populations showed differences in their composition that could contribute to this differential effect. Furthermore, the miRNAs present in 120k EVs were analysed and their potential interactions with human host genes was explored by computational target prediction. Different pathways involved in inflammation, immune response and apoptosis were identified as potentially targeted by the miRNAs present in this population of EVs. This is the first study showing specific roles for different EV populations in the pathogenesis of a parasitic helminth, and more importantly, an important advance towards deciphering the mechanisms used in establishment of opisthorchiasis and liver fluke infection-associated malignancy.\n                <\/jats:p>","DOI":"10.1101\/2023.05.22.540805","type":"posted-content","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T20:11:06Z","timestamp":1684786266000},"source":"Crossref","is-referenced-by-count":5,"title":["Small extracellular vesicles but not microvesicles from\n                  <i>Opisthorchis viverrini<\/i>\n                  promote cell proliferation in human cholangiocytes"],"prefix":"10.64898","author":[{"given":"Sujittra","family":"Chaiyadet","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Sotillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Smout","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martha","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise L.","family":"Doolan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley","family":"Waardenberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramon M.","family":"Eichenberger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matt","family":"Field","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul J.","family":"Brindley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thewarach","family":"Laha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Loukas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023052409551060000_2023.05.22.540805v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2010.07.006"},{"key":"2023052409551060000_2023.05.22.540805v1.2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040201"},{"key":"2023052409551060000_2023.05.22.540805v1.3","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv291"},{"key":"2023052409551060000_2023.05.22.540805v1.4","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200900393"},{"key":"2023052409551060000_2023.05.22.540805v1.5","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/bs.apar.2018.10.001","article-title":"Update on Pathogenesis of Opisthorchiasis and Cholangiocarcinoma","volume":"102","year":"2018","journal-title":"Adv Parasitol"},{"key":"2023052409551060000_2023.05.22.540805v1.6","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/bs.apar.2018.06.002","article-title":"Opisthorchis viverrini Proteome and Host-Parasite Interactions","volume":"102","year":"2018","journal-title":"Adv Parasitol"},{"issue":"5","key":"2023052409551060000_2023.05.22.540805v1.7","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.neo.2020.02.004","article-title":"Liver fluke granulin promotes extracellular vesicle-mediated crosstalk and cellular microenvironment conducive to cholangiocarcinoma","volume":"22","year":"2020","journal-title":"Neoplasia"},{"key":"2023052409551060000_2023.05.22.540805v1.8","doi-asserted-by":"crossref","unstructured":"Arunsan P , Ittiprasert W , Smout MJ , Cochran CJ , Mann VH , Chaiyadet S , et al. Programmed knockout mutation of liver fluke granulin attenuates virulence of infection-induced hepatobiliary morbidity. Elife. 2019;8.","DOI":"10.7554\/eLife.41463"},{"issue":"5","key":"2023052409551060000_2023.05.22.540805v1.9","doi-asserted-by":"crossref","first-page":"e0007450","DOI":"10.1371\/journal.pntd.0007450","article-title":"Vaccination of hamsters with Opisthorchis viverrini extracellular vesicles and vesicle-derived recombinant tetraspanins induces antibodies that block vesicle uptake by cholangiocytes and reduce parasite burden after challenge infection","volume":"13","year":"2019","journal-title":"PLoS Negl Trop Dis"},{"key":"2023052409551060000_2023.05.22.540805v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2014.11.004"},{"key":"2023052409551060000_2023.05.22.540805v1.11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005209"},{"key":"2023052409551060000_2023.05.22.540805v1.12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000611"},{"issue":"9","key":"2023052409551060000_2023.05.22.540805v1.13","doi-asserted-by":"crossref","first-page":"e1010839","DOI":"10.1371\/journal.ppat.1010839","article-title":"Knockout of liver fluke granulin, Ov-grn-1, impedes malignant transformation during chronic infection with Opisthorchis viverrini","volume":"18","year":"2022","journal-title":"PLoS Pathog"},{"issue":"1","key":"2023052409551060000_2023.05.22.540805v1.14","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","year":"2018","journal-title":"J Extracell Vesicles"},{"issue":"1","key":"2023052409551060000_2023.05.22.540805v1.15","doi-asserted-by":"crossref","first-page":"e12298","DOI":"10.1002\/jev2.12298","article-title":"Special considerations for studies of extracellular vesicles from parasitic helminths: A community-led roadmap to increase rigour and reproducibility","volume":"12","year":"2023","journal-title":"J Extracell Vesicles"},{"key":"2023052409551060000_2023.05.22.540805v1.16","doi-asserted-by":"crossref","unstructured":"Doyle LM , Wang MZ . Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells. 2019;8(7).","DOI":"10.3390\/cells8070727"},{"key":"2023052409551060000_2023.05.22.540805v1.17","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M115.053934"},{"key":"2023052409551060000_2023.05.22.540805v1.18","doi-asserted-by":"crossref","unstructured":"Kifle DW , Pearson MS , Becker L , Pickering D , Loukas A , Sotillo J . Proteomic analysis of two populations of Schistosoma mansoni-derived extracellular vesicles: 15k pellet and 120k pellet vesicles. Mol Biochem Parasitol. 2020;236:111264.","DOI":"10.1016\/j.molbiopara.2020.111264"},{"issue":"9","key":"2023052409551060000_2023.05.22.540805v1.19","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.ijpara.2020.04.010","article-title":"The protein and microRNA cargo of extracellular vesicles from parasitic helminths current status and research priorities","volume":"50","year":"2020","journal-title":"Int J Parasitol"},{"issue":"3","key":"2023052409551060000_2023.05.22.540805v1.20","first-page":"378","article-title":"Schistosomal MicroRNAs Isolated From Extracellular Vesicles in Sera of Infected Patients: A New Tool for Diagnosis and Follow-up of Human Schistosomiasis","volume":"215","year":"2017","journal-title":"J Infect Dis"},{"key":"2023052409551060000_2023.05.22.540805v1.21","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00850"},{"key":"2023052409551060000_2023.05.22.540805v1.22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007817"},{"issue":"1","key":"2023052409551060000_2023.05.22.540805v1.23","doi-asserted-by":"crossref","first-page":"e47882","DOI":"10.15252\/embr.201947882","article-title":"Schistosomal extracellular vesicle-enclosed miRNAs modulate host T helper cell differentiation","volume":"21","year":"2020","journal-title":"EMBO Rep"},{"issue":"1","key":"2023052409551060000_2023.05.22.540805v1.24","doi-asserted-by":"crossref","first-page":"1785738","DOI":"10.1080\/20013078.2020.1785738","article-title":"Sja-miR-71a in Schistosome egg-derived extracellular vesicles suppresses liver fibrosis caused by schistosomiasis via targeting semaphorin 4D","volume":"9","year":"2020","journal-title":"J Extracell Vesicles"},{"key":"2023052409551060000_2023.05.22.540805v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2015.09.002"},{"key":"2023052409551060000_2023.05.22.540805v1.26","doi-asserted-by":"crossref","unstructured":"Chaiyadet S , Sotillo J , Krueajampa W , Thongsen S , Smout M , Brindley PJ , et al. Silencing of Opisthorchis viverrini Tetraspanin Gene Expression Results in Reduced Secretion of Extracellular Vesicles. Front Cell Infect Microbiol. 2022;12:827521.","DOI":"10.3389\/fcimb.2022.827521"},{"key":"2023052409551060000_2023.05.22.540805v1.27","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M114.038950"},{"key":"2023052409551060000_2023.05.22.540805v1.28","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bth092"},{"key":"2023052409551060000_2023.05.22.540805v1.29","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6277"},{"key":"2023052409551060000_2023.05.22.540805v1.30","doi-asserted-by":"publisher","DOI":"10.1021\/pr101196n"},{"key":"2023052409551060000_2023.05.22.540805v1.31","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201000595"},{"key":"2023052409551060000_2023.05.22.540805v1.32","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3109"},{"key":"2023052409551060000_2023.05.22.540805v1.33","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1106"},{"key":"2023052409551060000_2023.05.22.540805v1.34","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn176"},{"key":"2023052409551060000_2023.05.22.540805v1.35","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1217"},{"key":"2023052409551060000_2023.05.22.540805v1.36","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"2023052409551060000_2023.05.22.540805v1.37","doi-asserted-by":"crossref","unstructured":"Waardenberg AJ , Field MA . consensusDE: an R package for assessing consensus of multiple RNA-seq algorithms with RUV correction. PeerJ. 2019;7:e8206.","DOI":"10.7717\/peerj.8206"},{"key":"2023052409551060000_2023.05.22.540805v1.38","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr669"},{"key":"2023052409551060000_2023.05.22.540805v1.39","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.17.3389"},{"key":"2023052409551060000_2023.05.22.540805v1.40","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5378"},{"key":"2023052409551060000_2023.05.22.540805v1.41","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr688"},{"key":"2023052409551060000_2023.05.22.540805v1.42","unstructured":"Kanellos I , Vergoulis T , Sacharidis D , Dalamagas T , Hatzigeorgiou A , Sartzetakis S , et al. MR microT: a MapReduce-based MicroRNA target prediction method. Proceedings of the 26th International Conference on Scientific and Statistical Database Management; Aalborg, Denmark: Association for Computing Machinery; 2014. p. Article 47."},{"key":"2023052409551060000_2023.05.22.540805v1.43","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz757"},{"key":"2023052409551060000_2023.05.22.540805v1.44","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2003-5-1-r1"},{"key":"2023052409551060000_2023.05.22.540805v1.45","doi-asserted-by":"publisher","DOI":"10.1038\/s41596&ndash;019&ndash;0128&ndash;8"},{"key":"2023052409551060000_2023.05.22.540805v1.46","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1994.266.6.G1060"},{"key":"2023052409551060000_2023.05.22.540805v1.47","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b00047"},{"key":"2023052409551060000_2023.05.22.540805v1.48","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b00898"},{"key":"2023052409551060000_2023.05.22.540805v1.49","doi-asserted-by":"crossref","unstructured":"Webber J , Clayton A . How pure are your vesicles? J Extracell Vesicles. 2013;2.","DOI":"10.3402\/jev.v2i0.19861"},{"key":"2023052409551060000_2023.05.22.540805v1.50","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17020170"},{"key":"2023052409551060000_2023.05.22.540805v1.51"},{"issue":"5","key":"2023052409551060000_2023.05.22.540805v1.52","doi-asserted-by":"crossref","first-page":"e12213","DOI":"10.1002\/jev2.12213","article-title":"Tetraspanins distinguish separate extracellular vesicle subpopulations in human serum and plasma Contributions of platelet extracellular vesicles in plasma samples","volume":"11","year":"2022","journal-title":"J Extracell Vesicles"},{"key":"2023052409551060000_2023.05.22.540805v1.53","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008090"},{"key":"2023052409551060000_2023.05.22.540805v1.54","doi-asserted-by":"crossref","unstructured":"Munir J , Yoon JK , Ryu S . Therapeutic miRNA-Enriched Extracellular Vesicles: Current Approaches and Future Prospects. Cells. 2020;9(10).","DOI":"10.3390\/cells9102271"},{"key":"2023052409551060000_2023.05.22.540805v1.55","doi-asserted-by":"crossref","unstructured":"Eichenberger RM , Sotillo J , Loukas A . Immunobiology of parasitic worm extracellular vesicles. Immunol Cell Biol. 2018.","DOI":"10.1111\/imcb.12171"},{"key":"2023052409551060000_2023.05.22.540805v1.56","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2018.08.002"},{"key":"2023052409551060000_2023.05.22.540805v1.57","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2014.02.012"},{"key":"2023052409551060000_2023.05.22.540805v1.58","first-page":"812141","article-title":"Role of Fasciola hepatica Small RNAs in the Interaction With the Mammalian Host","volume":"11","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"2023052409551060000_2023.05.22.540805v1.59","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2015.06.002"},{"key":"2023052409551060000_2023.05.22.540805v1.60","doi-asserted-by":"crossref","first-page":"28665","DOI":"10.3402\/jev.v4.28665","article-title":"Protein and small non-coding RNA-enriched extracellular vesicles are released by the pathogenic blood fluke Schistosoma mansoni","volume":"4","year":"2015","journal-title":"J Extracell Vesicles"},{"issue":"1","key":"2023052409551060000_2023.05.22.540805v1.61","doi-asserted-by":"crossref","first-page":"3286","DOI":"10.1038\/s41598-018-21587-4","article-title":"Vesicle-based secretion in schistosomes: Analysis of protein and microRNA (miRNA) content of exosome-like vesicles derived from Schistosoma mansoni","volume":"8","year":"2018","journal-title":"Sci Rep"},{"key":"2023052409551060000_2023.05.22.540805v1.62","doi-asserted-by":"publisher","DOI":"10.1038\/srep25885"},{"issue":"1","key":"2023052409551060000_2023.05.22.540805v1.63","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1186\/s13071-016-1845-2","article-title":"Release of extracellular vesicles containing small RNAs from the eggs of Schistosoma japonicum","volume":"9","year":"2016","journal-title":"Parasit Vectors"},{"key":"2023052409551060000_2023.05.22.540805v1.64","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-014-4127-y"},{"key":"2023052409551060000_2023.05.22.540805v1.65","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2014.12.003"},{"key":"2023052409551060000_2023.05.22.540805v1.66","doi-asserted-by":"crossref","unstructured":"Macchiaroli N , Cucher M , Zarowiecki M , Maldonado L , Kamenetzky L , Rosenzvit MC . microRNA profiling in the zoonotic parasite Echinococcus canadensis using a high-throughput approach. Parasit Vectors. 2015;8:83.","DOI":"10.1186\/s13071-015-0686-8"},{"issue":"1","key":"2023052409551060000_2023.05.22.540805v1.67","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1186\/s12864-022-08644-z","article-title":"Stage-specific miRNAs regulate gene expression associated with growth, development and parasite-host interaction during the intra-mammalian migration of the zoonotic helminth parasite Fasciola hepatica","volume":"23","year":"2022","journal-title":"BMC Genomics"},{"key":"2023052409551060000_2023.05.22.540805v1.68","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2014.12.004"},{"key":"2023052409551060000_2023.05.22.540805v1.69","doi-asserted-by":"crossref","unstructured":"Suo L , Chang X , Xu N , Ji H . The Anti-proliferative Activity of GnRH Through Downregulation of the Akt\/ERK Pathways in Pancreatic Cancer. Front Endocrinol (Lausanne). 2019;10:370.","DOI":"10.3389\/fendo.2019.00370"},{"key":"2023052409551060000_2023.05.22.540805v1.70","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2012.09.023"},{"issue":"1","key":"2023052409551060000_2023.05.22.540805v1.71","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s12957-022-02511-7","article-title":"The VEGF expression associated with prognosis in patients with intrahepatic cholangiocarcinoma: a systematic review and meta-analysis","volume":"20","year":"2022","journal-title":"World J Surg Oncol"},{"key":"2023052409551060000_2023.05.22.540805v1.72","doi-asserted-by":"crossref","unstructured":"Simone V , Brunetti O , Lupo L , Testini M , Maiorano E , Simone M , et al. Targeting Angiogenesis in Biliary Tract Cancers: An Open Option. Int J Mol Sci. 2017;18(2).","DOI":"10.3390\/ijms18020418"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.05.22.540805","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T04:41:02Z","timestamp":1768452062000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2023.05.22.540805"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,22]]},"references-count":72,"URL":"https:\/\/doi.org\/10.1101\/2023.05.22.540805","relation":{},"subject":[],"published":{"date-parts":[[2023,5,22]]},"subtype":"preprint"}}