{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T18:23:51Z","timestamp":1793125431744,"version":"4.5.0"},"reference-count":95,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,4,19]],"date-time":"2024-04-19T00:00:00Z","timestamp":1713484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo (FAPESP) Thematic","doi-asserted-by":"publisher","award":["2018\/23693-5"],"award-info":[{"award-number":["2018\/23693-5"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo (FAPESP) Thematic","doi-asserted-by":"publisher","award":["148745\/2022-9"],"award-info":[{"award-number":["148745\/2022-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo (FAPESP) Thematic","doi-asserted-by":"publisher","award":["306646\/2019-6"],"award-info":[{"award-number":["306646\/2019-6"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","award":["2018\/23693-5"],"award-info":[{"award-number":["2018\/23693-5"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","award":["148745\/2022-9"],"award-info":[{"award-number":["148745\/2022-9"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","award":["306646\/2019-6"],"award-info":[{"award-number":["306646\/2019-6"]}]},{"name":"CNPq","award":["2018\/23693-5"],"award-info":[{"award-number":["2018\/23693-5"]}]},{"name":"CNPq","award":["148745\/2022-9"],"award-info":[{"award-number":["148745\/2022-9"]}]},{"name":"CNPq","award":["306646\/2019-6"],"award-info":[{"award-number":["306646\/2019-6"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ncRNA"],"abstract":"<jats:p>Schistosomiasis is a disease caused by trematodes of the genus Schistosoma that affects over 200 million people worldwide. For decades, praziquantel (PZQ) has been the only available drug to treat the disease. Despite recent discoveries that identified a transient receptor ion channel as the target of PZQ, schistosome response to this drug remains incompletely understood, since effectiveness relies on other factors that may trigger a complex regulation of parasite gene expression. Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with low or no protein-coding potential that play important roles in S. mansoni homeostasis, reproduction, and fertility. Here, we show that in vivo PZQ treatment modulates lncRNA levels in S. mansoni. We re-analyzed public RNA-Seq data from mature and immature S. mansoni worms treated in vivo with PZQ and detected hundreds of lncRNAs differentially expressed following drug exposure, many of which are shared among mature and immature worms. Through RT-qPCR, seven out of ten selected lncRNAs were validated as differentially expressed; interestingly, we show that these lncRNAs are not adult worm stage-specific and are co-expressed with PZQ-modulated protein-coding genes. By demonstrating that parasite lncRNA expression levels alter in response to PZQ, this study unravels an important step toward elucidating the complex mechanisms of S. mansoni response to PZQ.<\/jats:p>","DOI":"10.3390\/ncrna10020027","type":"journal-article","created":{"date-parts":[[2024,4,19]],"date-time":"2024-04-19T10:53:17Z","timestamp":1713523997000},"page":"27","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Long Non-Coding RNA Levels Are Modulated in Schistosoma mansoni following In Vivo Praziquantel Exposure"],"prefix":"10.3390","volume":"10","author":[{"given":"Pedro","family":"Jardim Poli","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Ciclo Celular, Instituto Butantan, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agatha","family":"Fischer-Carvalho","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ciclo Celular, Instituto Butantan, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7036-7305","authenticated-orcid":false,"given":"Ana Carolina","family":"Tahira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ciclo Celular, Instituto Butantan, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Chan","sequence":"additional","affiliation":[{"name":"Global Health Institute, University of Wisconsin-Madison, Madison, WI 53792, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6356-2401","authenticated-orcid":false,"given":"Sergio","family":"Verjovski-Almeida","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ciclo Celular, Instituto Butantan, S\u00e3o Paulo 05503-900, SP, Brazil"},{"name":"Instituto de Qu\u00edmica, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4999-5099","authenticated-orcid":false,"given":"Murilo","family":"Sena Amaral","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ciclo Celular, Instituto Butantan, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1016\/S0140-6736(13)61949-2","article-title":"Human schistosomiasis","volume":"383","author":"Colley","year":"2014","journal-title":"Lancet"},{"key":"ref_2","unstructured":"WHO (2024, January 09). Fact Sheets: Schistosomiasis; 2023. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/schistosomiasis."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zacharia, A., Mushi, V., and Makene, T. (2020). A systematic review and meta-analysis on the rate of human schistosomiasis reinfection. PLoS ONE, 15.","DOI":"10.1101\/2020.07.18.20156703"},{"key":"ref_4","unstructured":"WHO (2024, January 09). Global Health Estimates 2020: Disease Burden by Cause, Age, Sex, by Country and by Region, 2000\u20132019. Geneva, World Health Organization. Available online: https:\/\/www.who.int\/data\/gho\/data\/themes\/mortality-and-global-health-estimates\/global-health-estimates-leading-causes-of-dalys."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41572-018-0013-8","article-title":"Schistosomiasis","volume":"4","author":"McManus","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e02582-16","DOI":"10.1128\/AAC.02582-16","article-title":"Praziquantel for Schistosomiasis: Single-Drug Metabolism Revisited, Mode of Action, and Resistance","volume":"61","author":"Vale","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/978-1-4939-0915-5_3","article-title":"Schistosomiasis","volume":"766","author":"Lewis","year":"2014","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1017\/S0031182020000049","article-title":"Schistosomiasis then and now: What has changed in the last 100 years?","volume":"147","author":"Wilson","year":"2020","journal-title":"Parasitology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"eabj5832","DOI":"10.1126\/scitranslmed.abj5832","article-title":"Mechanism of praziquantel action at a parasitic flatworm ion channel","volume":"13","author":"Park","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"eabj9114","DOI":"10.1126\/scitranslmed.abj9114","article-title":"Genetic analysis of praziquantel response in schistosome parasites implicates a transient receptor potential channel","volume":"13","author":"Chevalier","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"McCusker, P., Rohr, C.M., and Chan, J.D. (2021). Schistosoma mansoni alter transcription of immunomodulatory gene products following in vivo praziquantel exposure. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009200"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nrg.2015.10","article-title":"Unique features of long non-coding RNA biogenesis and function","volume":"17","author":"Quinn","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/nrm.2017.104","article-title":"The functions and unique features of long intergenic non-coding RNA","volume":"19","author":"Ransohoff","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/s41580-020-00315-9","article-title":"Gene regulation by long non-coding RNAs and its biological functions","volume":"22","author":"Statello","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.cell.2018.01.011","article-title":"Functional Classification and Experimental Dissection of Long Noncoding RNAs","volume":"172","author":"Kopp","year":"2018","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s12943-020-01162-0","article-title":"Long non-coding RNAs regulate drug resistance in cancer","volume":"19","author":"Liu","year":"2020","journal-title":"Mol. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"21963","DOI":"10.1073\/pnas.1915690116","article-title":"Linking long noncoding RNA to drug resistance","volume":"116","author":"Smallegan","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1101\/gr.214205.116","article-title":"Chromatin environment, transcriptional regulation, and splicing distinguish lincRNAs and mRNAs","volume":"27","author":"Mattioli","year":"2017","journal-title":"Genome Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1007\/s00436-021-07384-5","article-title":"Long non-coding RNAs as possible therapeutic targets in protozoa, and in Schistosoma and other helminths","volume":"121","author":"Silveira","year":"2022","journal-title":"Parasitol Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/s41573-021-00219-z","article-title":"Noncoding RNA therapeutics-challenges and potential solutions","volume":"20","author":"Winkle","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1590\/S0001-37652011000200026","article-title":"Non-coding RNAs in schistosomes: An unexplored world","volume":"83","author":"Oliveira","year":"2011","journal-title":"An. Acad. Bras. Cienc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1080\/15476286.2020.1729594","article-title":"LncRNAs in molluscan and mammalian stages of parasitic schistosomes are developmentally-regulated and coordinately expressed with protein-coding genes","volume":"17","author":"Kim","year":"2020","journal-title":"RNA Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"21565","DOI":"10.1038\/s41598-020-78669-5","article-title":"Long non-coding RNA levels can be modulated by 5-azacytidine in Schistosoma mansoni","volume":"10","author":"Amaral","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Silveira, G.O., Coelho, H.S., Pereira, A.S.A., Miyasato, P.A., Santos, D.W., Maciel, L.F., Olberg, G.G.G., Tahira, A.C., Nakano, E., and Oliveira, M.L.S. (2023). Long non-coding RNAs are essential for Schistosoma mansoni pairing-dependent adult worm homeostasis and fertility. PLoS Pathog., 19.","DOI":"10.1371\/journal.ppat.1011369"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1080\/15476286.2019.1649584","article-title":"D-lnc: A comprehensive database and analytical platform to dissect the modification of drugs on lncRNA expression","volume":"16","author":"Jiang","year":"2019","journal-title":"RNA Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"823","DOI":"10.3389\/fgene.2019.00823","article-title":"Weighted Gene Co-Expression Analyses Point to Long Non-Coding RNA Hub Genes at Different Schistosoma mansoni Life-Cycle Stages","volume":"10","author":"Maciel","year":"2019","journal-title":"Front. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1038\/ncomms1433","article-title":"Cytosine methylation regulates oviposition in the pathogenic blood fluke Schistosoma mansoni","volume":"2","author":"Geyer","year":"2011","journal-title":"Nat. Commun."},{"key":"ref_28","first-page":"2701","article-title":"Mechanism of 5-azacytidine-induced transfer RNA cytosine-5-methyltransferase deficiency","volume":"40","author":"Lu","year":"1980","journal-title":"Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/0022-2836(82)90395-3","article-title":"Mechanism of action of eukaryotic DNA methyltransferase. Use of 5-azacytosine-containing DNA","volume":"162","author":"Taylor","year":"1982","journal-title":"J. Mol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.ijpddr.2018.03.006","article-title":"The anti-fecundity effect of 5-azacytidine (5-AzaC) on Schistosoma mansoni is linked to dis-regulated transcription, translation and stem cell activities","volume":"8","author":"Geyer","year":"2018","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"16816","DOI":"10.1038\/s41598-021-96055-7","article-title":"Assessment of reference genes at six different developmental stages of Schistosoma mansoni for quantitative RT-PCR","volume":"11","author":"Silveira","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Langfelder, P., and Horvath, S. (2008). WGCNA: An R package for weighted correlation network analysis. BMC Bioinform., 9.","DOI":"10.1186\/1471-2105-9-559"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"924877","DOI":"10.3389\/fgene.2022.924877","article-title":"Single-cell RNA-seq analyses show that long non-coding RNAs are conspicuously expressed in Schistosoma mansoni gamete and tegument progenitor cell populations","volume":"13","author":"Zhao","year":"2022","journal-title":"Front. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.biochi.2014.10.015","article-title":"Comparative biochemical analysis of three members of the Schistosoma mansoni TAL family: Differences in ion and drug binding properties","volume":"108","author":"Thomas","year":"2015","journal-title":"Biochimie"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.molbiopara.2018.02.002","article-title":"The tegumental allergen-like proteins of Schistosoma mansoni: A biochemical study of SmTAL4-TAL13","volume":"221","author":"Carson","year":"2018","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1042\/BST20150270","article-title":"A mysterious family of calcium-binding proteins from parasitic worms","volume":"44","author":"Thomas","year":"2016","journal-title":"Biochem. Soc. Trans."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"D1393","DOI":"10.1093\/nar\/gkad1042","article-title":"ncRNADrug: A database for validated and predicted ncRNAs associated with drug resistance and targeted by drugs","volume":"52","author":"Cao","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"18332","DOI":"10.1038\/s41598-022-22822-9","article-title":"Identification of repurposed drugs targeting significant long non-coding RNAs in the cross-talk between diabetes mellitus and Alzheimer\u2019s disease","volume":"12","author":"Ghiam","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Chen, H., Zhang, Z., and Zhang, J. (2022). In silico drug repositioning based on integrated drug targets and canonical correlation analysis. BMC Med. Genomics, 15.","DOI":"10.1186\/s12920-022-01203-1"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Guo, H., Liu, J., Ben, Q., Qu, Y., Li, M., Wang, Y., Chen, W., and Zhang, J. (2016). The aspirin-induced long non-coding RNA OLA1P2 blocks phosphorylated STAT3 homodimer formation. Genome Biol., 17.","DOI":"10.1186\/s13059-016-0892-5"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1002\/j.1460-2075.1987.tb02565.x","article-title":"The highly conserved amino-terminal region of the protein encoded by the v-myb oncogene functions as a DNA-binding domain","volume":"6","author":"Klempnauer","year":"1987","journal-title":"EMBO J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/335835a0","article-title":"Viral myb oncogene encodes a sequence-specific DNA-binding activity","volume":"335","author":"Biedenkapp","year":"1988","journal-title":"Nature"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/nrm1314","article-title":"The SANT domain: A unique histone-tail-binding module?","volume":"5","author":"Boyer","year":"2004","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Beesley, N.J., Cwiklinski, K., Allen, K., Hoyle, R.C., Spithill, T.W., La Course, E.J., Williams, D.J.L., Paterson, S., and Hodgkinson, J.E. (2023). A major locus confers triclabendazole resistance in Fasciola hepatica and shows dominant inheritance. PLoS Pathog., 19.","DOI":"10.1371\/journal.ppat.1011081"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Chalmers, I.W., Fitzsimmons, C.M., Brown, M., Pierrot, C., Jones, F.M., Wawrzyniak, J.M., Fernandez-Fuentes, N., Tukahebwa, E.M., Dunne, D.W., and Khalife, J. (2015). Human IgG1 Responses to Surface Localised Schistosoma mansoni Ly6 Family Members Drop following Praziquantel Treatment. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003920"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e12592","DOI":"10.1111\/pim.12592","article-title":"Schistosoma mansoni schistosomula antigens induce Th1\/Pro-inflammatory cytokine responses","volume":"40","author":"Egesa","year":"2018","journal-title":"Parasite Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Farias, L.P., Krautz-Peterson, G., Tararam, C.A., Araujo-Montoya, B.O., Fraga, T.R., Rofatto, H.K., Silva, F.P., Isaac, L., Da\u2019dara, A.A., and Wilson, R.A. (2013). On the three-finger protein domain fold and CD59-like proteins in Schistosoma mansoni. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002482"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"595","DOI":"10.5483\/BMBRep.2012.45.11.210","article-title":"Characterization and function of human Ly-6\/uPAR molecules","volume":"45","author":"Kong","year":"2012","journal-title":"BMB Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s40246-016-0074-2","article-title":"Organization, evolution and functions of the human and mouse Ly6\/uPAR family genes","volume":"10","author":"Loughner","year":"2016","journal-title":"Hum. Genomics"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/0014-4894(78)90156-X","article-title":"Schistosoma mansoni: Physical and chemical factors affecting the mechanical properties of the adult male musculature","volume":"46","author":"Fetterer","year":"1978","journal-title":"Exp. Parasitol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1093\/infdis\/151.6.1130","article-title":"Effects of praziquantel on different developmental stages of Schistosoma mansoni in vitro and in vivo","volume":"151","author":"Xiao","year":"1985","journal-title":"J. Infect. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1093\/jac\/dkt491","article-title":"The little we know about the pharmacokinetics and pharmacodynamics of praziquantel (racemate and R-enantiomer)","volume":"69","author":"Olliaro","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Panic, G., Ruf, M.T., and Keiser, J. (2017). Immunohistochemical Investigations of Treatment with Ro 13-3978, Praziquantel, Oxamniquine, and Mefloquine in Schistosoma mansoni-Infected Mice. Antimicrob. Agents. Chemother., 61.","DOI":"10.1128\/AAC.01142-17"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Reimers, N., Homann, A., Hoschler, B., Langhans, K., Wilson, R.A., Pierrot, C., Khalife, J., Grevelding, C.G., Chalmers, I.W., and Yazdanbakhsh, M. (2015). Drug-induced exposure of Schistosoma mansoni antigens SmCD59a and SmKK7. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003593"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Morais, S.B., Figueiredo, B.C., Assis, N.R.G., Alvarenga, D.M., de Magalhaes, M.T.Q., Ferreira, R.S., Vieira, A.T., Menezes, G.B., and Oliveira, S.C. (2018). Schistosoma mansoni SmKI-1 serine protease inhibitor binds to elastase and impairs neutrophil function and inflammation. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1006870"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1080\/17425255.2021.1887139","article-title":"The role of non-coding RNAs in ABC transporters regulation and their clinical implications of multidrug resistance in cancer","volume":"17","author":"Wang","year":"2021","journal-title":"Expert. Opin. Drug Metab. Toxicol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11033-021-06603-7","article-title":"LncRNA as a multifunctional regulator in cancer multi-drug resistance","volume":"48","author":"He","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"561","DOI":"10.2478\/s11658-014-0212-6","article-title":"Regulation of lncRNA expression","volume":"19","author":"Wu","year":"2014","journal-title":"Cell Mol. Biol. Lett."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.biochi.2015.03.001","article-title":"Long noncoding RNA turnover","volume":"117","author":"Yoon","year":"2015","journal-title":"Biochimie"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"371","DOI":"10.4161\/rna.23716","article-title":"microRNAs in parasites and parasite infection","volume":"10","author":"Zheng","year":"2013","journal-title":"RNA Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.ijpddr.2014.03.001","article-title":"microRNAs of parasitic helminths-Identification, characterization and potential as drug targets","volume":"4","author":"Britton","year":"2014","journal-title":"Int. J. Parasitol. Drugs Drug. Resist."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Tritten, L., Burkman, E., Moorhead, A., Satti, M., Geary, J., Mackenzie, C., and Geary, T. (2014). Detection of circulating parasite-derived microRNAs in filarial infections. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0002971"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"17594","DOI":"10.1038\/s41598-019-54154-6","article-title":"Profiling microRNAs through development of the parasitic nematode Haemonchus identifies nematode-specific miRNAs that suppress larval development","volume":"9","author":"Marks","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_64","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","author":"Meningher","year":"2020","journal-title":"EMBO Rep."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Liu, J., Zhu, L., Wang, J., Qiu, L., Chen, Y., Davis, R.E., and Cheng, G. (2019). Schistosoma japonicum extracellular vesicle miRNA cargo regulates host macrophage functions facilitating parasitism. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007817"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Leija-Montoya, A.G., Gonzalez-Ramirez, J., Martinez-Coronilla, G., Mejia-Leon, M.E., Isiordia-Espinoza, M., Sanchez-Munoz, F., Chavez-Cortez, E.G., Pitones-Rubio, V., and Serafin-Higuera, N. (2022). Roles of microRNAs and Long Non-Coding RNAs Encoded by Parasitic Helminths in Human Carcinogenesis. Int J. Mol. Sci, 23.","DOI":"10.3390\/ijms23158173"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Shao, C.C., Xu, M.J., Alasaad, S., Song, H.Q., Peng, L., Tao, J.P., and Zhu, X.Q. (2014). Comparative analysis of microRNA profiles between adult Ascaris lumbricoides and Ascaris suum. BMC Vet. Res., 10.","DOI":"10.1186\/1746-6148-10-99"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Fontenla, S., Rinaldi, G., Smircich, P., and Tort, J.F. (2017). Conservation and diversification of small RNA pathways within flatworms. BMC Evol. Biol., 17.","DOI":"10.1186\/s12862-017-1061-5"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.ijpara.2018.07.005","article-title":"Identification and expression profiling of microRNAs in Hymenolepis","volume":"49","author":"Macchiaroli","year":"2019","journal-title":"Int. J. Parasitol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2826","DOI":"10.1093\/gbe\/evx197","article-title":"Gain and Loss of Small RNA Classes-Characterization of Small RNAs in the Parasitic Nematode Family Strongyloididae","volume":"9","author":"Holz","year":"2017","journal-title":"Genome Biol. Evol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.actatropica.2016.03.036","article-title":"De novo assembly and characterization of the Trichuris trichiura adult worm transcriptome using Ion Torrent sequencing","volume":"159","author":"Santos","year":"2016","journal-title":"Acta Tropica."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1016\/j.ygeno.2019.07.016","article-title":"Genome-wide identification and characterization of long intergenic noncoding RNAs in the regenerative flatworm Macrostomum lignano","volume":"112","author":"Azlan","year":"2020","journal-title":"Genomics"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1534\/g3.116.028175","article-title":"Comparative and Transcriptome Analyses Uncover Key Aspects of Coding- and Long Noncoding RNAs in Flatworm Mitochondrial Genomes","volume":"6","author":"Ross","year":"2016","journal-title":"G3"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Rodelsperger, C., Menden, K., Serobyan, V., Witte, H., and Baskaran, P. (2016). First insights into the nature and evolution of antisense transcription in nematodes. BMC Evol. Biol., 16.","DOI":"10.1186\/s12862-016-0740-y"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Wei, S., Chen, H., Dzakah, E.E., Yu, B., Wang, X., Fu, T., Li, J., Liu, L., Fang, S., and Liu, W. (2019). Systematic evaluation of C. elegans lincRNAs with CRISPR knockout mutants. Genome Biol., 20.","DOI":"10.1186\/s13059-018-1619-6"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"6181","DOI":"10.1038\/s41467-021-26497-0","article-title":"Rhesus macaques self-curing from a schistosome infection can display complete immunity to challenge","volume":"12","author":"Amaral","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_77","unstructured":"Andrews, S. (2023, December 01). FastQC: A Quality Control Analysis Tool for High Throughput Sequencing Data, 0.11.9; 2010. Available online: https:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"fastp: An ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Li, B., and Dewey, C.N. (2011). RSEM: Accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-323"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: A Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_82","first-page":"1438","article-title":"From reads to genes to pathways: Differential expression analysis of RNA-Seq experiments using Rsubread and the edgeR quasi-likelihood pipeline","volume":"5","author":"Chen","year":"2016","journal-title":"F1000Res"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4288","DOI":"10.1093\/nar\/gks042","article-title":"Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation","volume":"40","author":"McCarthy","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e97","DOI":"10.1093\/nar\/gkv412","article-title":"Why weight? Modelling sample and observational level variability improves power in RNA-seq analyses","volume":"43","author":"Liu","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e161","DOI":"10.1093\/nar\/gku864","article-title":"svaseq: Removing batch effects and other unwanted noise from sequencing data","volume":"42","author":"Leek","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Dos Santos, K.C.G., Desgagn\u00e9-Penix, I., and Germain, H. (2020). Custom selected reference genes outperform pre-defined reference genes in transcriptomic analysis. BMC Genom., 21.","DOI":"10.1186\/s12864-019-6426-2"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"5245","DOI":"10.1158\/0008-5472.CAN-04-0496","article-title":"Normalization of real-time quantitative reverse transcription-PCR data: A model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets","volume":"64","author":"Andersen","year":"2004","journal-title":"Cancer Res."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Vandesompele, J., De Preter, K., Pattyn, F., Poppe, B., Van Roy, N., De Paepe, A., and Speleman, F. (2002). Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol, 3.","DOI":"10.1186\/gb-2002-3-7-research0034"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s10142-023-01055-7","article-title":"RefFinder: A web-based tool for comprehensively analyzing and identifying reference genes","volume":"23","author":"Xie","year":"2023","journal-title":"Funct. Integr. Genomics"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Pinheiro, J., and Bates, D. (2000). Mixed-Effects Models in S and S-PLUS, Springer.","DOI":"10.1007\/978-1-4419-0318-1"},{"key":"ref_92","unstructured":"Pinheiro, J., Bates, D., DebRoy, S., Sarkar, D., EISPACK_authors, Heisterkamp, S., Van_Willigen, B., Ranke, J., and R_Core_Team (2023, December 01). nlme: Linear and Nonlinear Mixed Effects Models. Available online: https:\/\/CRAN.R-project.org\/package=nlme."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Love, M.I., Huber, W., and Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol, 15.","DOI":"10.1186\/s13059-014-0550-8"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"ELIXIR-709","DOI":"10.12688\/f1000research.24956.2","article-title":"gprofiler2\u2014An R package for gene list functional enrichment analysis and namespace conversion toolset g:Profiler","volume":"9","author":"Kolberg","year":"2020","journal-title":"F1000Res"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Supek, F., Bosnjak, M., Skunca, N., and Smuc, T. (2011). REVIGO summarizes and visualizes long lists of gene ontology terms. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021800"}],"container-title":["Non-Coding RNA"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2311-553X\/10\/2\/27\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:31:12Z","timestamp":1760106672000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2311-553X\/10\/2\/27"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,19]]},"references-count":95,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["ncrna10020027"],"URL":"https:\/\/doi.org\/10.3390\/ncrna10020027","relation":{},"ISSN":["2311-553X"],"issn-type":[{"value":"2311-553X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,19]]}}}