{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:50:55Z","timestamp":1792612255972,"version":"4.5.0"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T00:00:00Z","timestamp":1608076800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T00:00:00Z","timestamp":1608076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI114748"],"award-info":[{"award-number":["R01AI114748"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["1I01BX002670"],"award-info":[{"award-number":["1I01BX002670"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["PR170067"],"award-info":[{"award-number":["PR170067"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>HOXA transcript antisense RNA myeloid-specific 1 (HOTAIRM1) is a long non-coding RNA (lncRNA) that plays a pivotal role in regulating myeloid cell development via targeting HOXA1 gene expression. We and others have previously shown that myeloid-derived suppressor cells (MDSCs), a heterogeneous population of immature myeloid cells, expand during chronic viral (HCV, HIV) infections. However, the role of HOTAIRM1 in the development and suppression of MDSCs during viral infection remains unknown. In this study, we demonstrate that the expressions of HOTAIRM1 and its target HOXA1 are substantially upregulated to promote the expressions of immunosuppressive molecules, including arginase 1, inducible nitric oxide synthase, signal transducer and activator of transcription 3, and reactive oxygen species, in CD33<jats:sup>+<\/jats:sup> myeloid cells derived from hepatitis C virus (HCV)-infected patients. We show that HCV-associated exosomes (HCV-Exo) can modulate HOTAIRM1, HOXA1, and miR124 expressions to regulate MDSC development. Importantly, overexpression of HOTAIRM1 or HOXA1 in healthy CD33<jats:sup>+<\/jats:sup> myeloid cells promoted the MDSC differentiation and suppressive functions; conversely, silencing of HOTAIRM1 or HOXA1 expression in MDSCs from HCV patients significantly reduced the MDSC frequency and their suppressive functions. In essence, these results indicate that the HOTAIRM1-HOXA1-miR124 axis enhances the differentiation and suppressive functions of MDSCs and may be a potential target for immunomodulation in conjunction with antiviral therapy during chronic viral infection.<\/jats:p>","DOI":"10.1038\/s41598-020-78786-1","type":"journal-article","created":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T11:24:50Z","timestamp":1608117890000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["LncRNA HOTAIRM1 promotes MDSC expansion and suppressive functions through the HOXA1-miR124 axis during HCV infection"],"prefix":"10.1038","volume":"10","author":[{"given":"Bal Krishna Chand","family":"Thakuri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lam N.","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lam N. T.","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushant","family":"Khanal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dechao","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xindi","family":"Dang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison","family":"Schank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao Y.","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng D.","family":"Morrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed El","family":"Gazzar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengke","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunbin","family":"Ning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan P.","family":"Moorman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi Q.","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,12,16]]},"reference":[{"key":"78786_CR1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.immuni.2013.12.010","volume":"40","author":"SH Park","year":"2014","unstructured":"Park, S. H. & Rehermann, B. Immune responses to HCV and other hepatitis viruses. Immunity 40, 13\u201324. https:\/\/doi.org\/10.1016\/j.immuni.2013.12.010 (2014).","journal-title":"Immunity"},{"key":"78786_CR2","doi-asserted-by":"publisher","first-page":"4121","DOI":"10.1172\/JCI67714","volume":"123","author":"HR Rosen","year":"2013","unstructured":"Rosen, H. R. Emerging concepts in immunity to hepatitis C virus infection. J Clin Invest 123, 4121\u20134130. https:\/\/doi.org\/10.1172\/JCI67714 (2013).","journal-title":"J Clin Invest"},{"key":"78786_CR3","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1038\/nrd4050","volume":"12","author":"MP Manns","year":"2013","unstructured":"Manns, M. P. & von Hahn, T. Novel therapies for hepatitis C\u2014one pill fits all?. Nat Rev Drug Discov 12, 595\u2013610. https:\/\/doi.org\/10.1038\/nrd4050 (2013).","journal-title":"Nat Rev Drug Discov"},{"key":"78786_CR4","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1053\/j.gastro.2016.04.003","volume":"151","author":"JM Pawlotsky","year":"2016","unstructured":"Pawlotsky, J. M. Hepatitis C virus resistance to direct-acting antiviral drugs in interferon-free regimens. Gastroenterology 151, 70\u201386. https:\/\/doi.org\/10.1053\/j.gastro.2016.04.003 (2016).","journal-title":"Gastroenterology"},{"key":"78786_CR5","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1093\/cid\/ciw111","volume":"62","author":"KN Ly","year":"2016","unstructured":"Ly, K. N., Hughes, E. M., Jiles, R. B. & Holmberg, S. D. Rising mortality associated with hepatitis C virus in the United States, 2003\u20132013. Clin Infect Dis 62, 1287\u20131288. https:\/\/doi.org\/10.1093\/cid\/ciw111 (2016).","journal-title":"Clin Infect Dis"},{"key":"78786_CR6","doi-asserted-by":"publisher","first-page":"4499","DOI":"10.4049\/jimmunol.0802740","volume":"182","author":"S Ostrand-Rosenberg","year":"2009","unstructured":"Ostrand-Rosenberg, S. & Sinha, P. Myeloid-derived suppressor cells: linking inflammation and cancer. J Immunol 182, 4499\u20134506. https:\/\/doi.org\/10.4049\/jimmunol.0802740 (2009).","journal-title":"J Immunol"},{"key":"78786_CR7","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1038\/nri2506","volume":"9","author":"DI Gabrilovich","year":"2009","unstructured":"Gabrilovich, D. I. & Nagaraj, S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9, 162\u2013174. https:\/\/doi.org\/10.1038\/nri2506 (2009).","journal-title":"Nat Rev Immunol"},{"key":"78786_CR8","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1159\/000368233","volume":"7","author":"J Dai","year":"2015","unstructured":"Dai, J., El Gazzar, M., Li, G. Y., Moorman, J. P. & Yao, Z. Q. Myeloid-derived suppressor cells: Paradoxical roles in infection and immunity. J Innate Immun 7, 116\u2013126. https:\/\/doi.org\/10.1159\/000368233 (2015).","journal-title":"J Innate Immun"},{"key":"78786_CR9","doi-asserted-by":"publisher","first-page":"e1003993","DOI":"10.1371\/journal.ppat.1003993","volume":"10","author":"NL Bowers","year":"2014","unstructured":"Bowers, N. L. et al. Immune suppression by neutrophils in HIV-1 infection: Role of PD-L1\/PD-1 pathway. PLoS Pathog 10, e1003993. https:\/\/doi.org\/10.1371\/journal.ppat.1003993 (2014).","journal-title":"PLoS Pathog"},{"key":"78786_CR10","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/j.immuni.2012.10.022","volume":"38","author":"BA Norris","year":"2013","unstructured":"Norris, B. A. et al. Chronic but not acute virus infection induces sustained expansion of myeloid suppressor cell numbers that inhibit viral-specific T cell immunity. Immunity 38, 309\u2013321 (2013).","journal-title":"Immunity"},{"key":"78786_CR11","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1002\/hep.24700","volume":"55","author":"RS Tacke","year":"2012","unstructured":"Tacke, R. S. et al. Myeloid suppressor cells induced by hepatitis C virus suppress T-cell responses through the production of reactive oxygen species. Hepatology 55, 343\u2013353. https:\/\/doi.org\/10.1002\/hep.24700 (2012).","journal-title":"Hepatology"},{"key":"78786_CR12","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1007\/s10875-012-9861-2","volume":"33","author":"W Cai","year":"2013","unstructured":"Cai, W. et al. Clinical significance and functional studies of myeloid-derived suppressor cells in chronic hepatitis C patients. J Clin Immunol 33, 798\u2013808. https:\/\/doi.org\/10.1007\/s10875-012-9861-2 (2013).","journal-title":"J Clin Immunol"},{"key":"78786_CR13","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1097\/QAD.0000000000001083","volume":"30","author":"L Wang","year":"2016","unstructured":"Wang, L. et al. Expansion of myeloid-derived suppressor cells promotes differentiation of regulatory T cells in HIV-1+ individuals. AIDS 30, 1521\u20131531. https:\/\/doi.org\/10.1097\/QAD.0000000000001083 (2016).","journal-title":"AIDS"},{"key":"78786_CR14","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1111\/imm.12616","volume":"148","author":"JP Ren","year":"2016","unstructured":"Ren, J. P. et al. Hepatitis C virus-induced myeloid-derived suppressor cells regulate T-cell differentiation and function via the signal transducer and activator of transcription 3 pathway. Immunology 148, 377\u2013386. https:\/\/doi.org\/10.1111\/imm.12616 (2016).","journal-title":"Immunology"},{"key":"78786_CR15","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1111\/imm.12680","volume":"150","author":"JP Ren","year":"2017","unstructured":"Ren, J. P. et al. Decline of miR-124 in myeloid cells promotes regulatory T-cell development in hepatitis C virus infection. Immunology 150, 213\u2013220. https:\/\/doi.org\/10.1111\/imm.12680 (2017).","journal-title":"Immunology"},{"key":"78786_CR16","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/s41421-018-0052-z","volume":"4","author":"L Wang","year":"2018","unstructured":"Wang, L. et al. HCV-associated exosomes promote myeloid-derived suppressor cell expansion via inhibiting miR-124 to regulate T follicular cell differentiation and function. Cell Discov 4, 51. https:\/\/doi.org\/10.1038\/s41421-018-0052-z (2018).","journal-title":"Cell Discov"},{"key":"78786_CR17","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1016\/j.tig.2017.08.002","volume":"33","author":"A Jandura","year":"2017","unstructured":"Jandura, A. & Krause, H. M. The new RNA world: Growing evidence for long noncoding RNA functionality. Trends Genet. 33, 665\u2013676 (2017).","journal-title":"Trends Genet."},{"key":"78786_CR18","doi-asserted-by":"publisher","first-page":"14744","DOI":"10.3390\/ijms140714744","volume":"14","author":"F Morceau","year":"2013","unstructured":"Morceau, F., Chateauvieux, S., Gaigneaux, A., Dicato, M. & Diederich, M. Long and short non-coding RNAs as regulators of hematopoietic differentiation. Int J Mol Sci 14, 14744\u201314770. https:\/\/doi.org\/10.3390\/ijms140714744 (2013).","journal-title":"Int J Mol Sci"},{"key":"78786_CR19","doi-asserted-by":"publisher","first-page":"103214","DOI":"10.1016\/j.bioorg.2019.103214","volume":"92","author":"X Zhang","year":"2019","unstructured":"Zhang, X., Hong, R., Chen, W., Xu, M. & Wang, L. The role of long noncoding RNA in major human disease. Bioorg Chem 92, 103214. https:\/\/doi.org\/10.1016\/j.bioorg.2019.103214 (2019).","journal-title":"Bioorg Chem"},{"key":"78786_CR20","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1038\/nature05874","volume":"447","author":"E Birney","year":"2007","unstructured":"Birney, E. et al. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447, 799\u2013816. https:\/\/doi.org\/10.1038\/nature05874 (2007).","journal-title":"Nature"},{"key":"78786_CR21","doi-asserted-by":"publisher","first-page":"1311","DOI":"10.1016\/j.cell.2007.05.022","volume":"129","author":"JL Rinn","year":"2007","unstructured":"Rinn, J. L. et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129, 1311\u20131323. https:\/\/doi.org\/10.1016\/j.cell.2007.05.022 (2007).","journal-title":"Cell"},{"key":"78786_CR22","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1016\/j.bbrc.2007.03.200","volume":"357","author":"YT Sasaki","year":"2007","unstructured":"Sasaki, Y. T., Sano, M., Kin, T., Asai, K. & Hirose, T. Coordinated expression of ncRNAs and HOX mRNAs in the human HOXA locus. Biochem Biophys Res Commun 357, 724\u2013730. https:\/\/doi.org\/10.1016\/j.bbrc.2007.03.200 (2007).","journal-title":"Biochem Biophys Res Commun"},{"key":"78786_CR23","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1261\/rna.266707","volume":"13","author":"L Sessa","year":"2007","unstructured":"Sessa, L. et al. Noncoding RNA synthesis and loss of Polycomb group repression accompanies the colinear activation of the human HOXA cluster. RNA 13, 223\u2013239. https:\/\/doi.org\/10.1261\/rna.266707 (2007).","journal-title":"RNA"},{"key":"78786_CR24","doi-asserted-by":"publisher","first-page":"2526","DOI":"10.1182\/blood-2008-06-162164","volume":"113","author":"X Zhang","year":"2009","unstructured":"Zhang, X. et al. A myelopoiesis-associated regulatory intergenic noncoding RNA transcript within the human HOXA cluster. Blood 113, 2526\u20132534. https:\/\/doi.org\/10.1182\/blood-2008-06-162164 (2009).","journal-title":"Blood"},{"key":"78786_CR25","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/0925-4773(92)90055-O","volume":"38","author":"AW Langston","year":"1992","unstructured":"Langston, A. W. & Gudas, L. J. Identification of a retinoic acid responsive enhancer 3\u2032 of the murine homeobox gene Hox-1.6. Mech. Dev. 38, 217\u2013227 (1992).","journal-title":"Mech. Dev."},{"key":"78786_CR26","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1038\/cdd.2016.111","volume":"24","author":"ZH Chen","year":"2017","unstructured":"Chen, Z. H. et al. The lncRNA HOTAIRM1 regulates the degradation of PML-RARA oncoprotein and myeloid cell differentiation by enhancing the autophagy pathway. Cell Death Differ 24, 212\u2013224. https:\/\/doi.org\/10.1038\/cdd.2016.111 (2017).","journal-title":"Cell Death Differ"},{"key":"78786_CR27","doi-asserted-by":"publisher","first-page":"777","DOI":"10.4161\/rna.28828","volume":"11","author":"X Zhang","year":"2014","unstructured":"Zhang, X., Weissman, S. M. & Newburger, P. E. Long intergenic non-coding RNA HOTAIRM1 regulates cell cycle progression during myeloid maturation in NB4 human promyelocytic leukemia cells. RNA Biol 11, 777\u2013787. https:\/\/doi.org\/10.4161\/rna.28828 (2014).","journal-title":"RNA Biol"},{"key":"78786_CR28","doi-asserted-by":"publisher","first-page":"473","DOI":"10.3389\/fimmu.2018.00473","volume":"9","author":"X Tian","year":"2018","unstructured":"Tian, X. et al. Long non-coding RNA HOXA transcript antisense RNA myeloid-specific 1-HOXA1 Axis downregulates the immunosuppressive activity of myeloid-derived suppressor cells in lung cancer. Front Immunol 9, 473. https:\/\/doi.org\/10.3389\/fimmu.2018.00473 (2018).","journal-title":"Front Immunol"},{"key":"78786_CR29","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1186\/s13046-018-0941-x","volume":"37","author":"Q Li","year":"2018","unstructured":"Li, Q., Dong, C., Cui, J., Wang, Y. & Hong, X. Over-expressed lncRNA HOTAIRM1 promotes tumor growth and invasion through up-regulating HOXA1 and sequestering G9a\/EZH2\/Dnmts away from the HOXA1 gene in glioblastoma multiforme. J Exp Clin Cancer Res 37, 265. https:\/\/doi.org\/10.1186\/s13046-018-0941-x (2018).","journal-title":"J Exp Clin Cancer Res"},{"key":"78786_CR30","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1093\/nar\/gkw966","volume":"45","author":"XQ Wang","year":"2017","unstructured":"Wang, X. Q. & Dostie, J. Reciprocal regulation of chromatin state and architecture by HOTAIRM1 contributes to temporal collinear HOXA gene activation. Nucleic Acids Res 45, 1091\u20131104. https:\/\/doi.org\/10.1093\/nar\/gkw966 (2017).","journal-title":"Nucleic Acids Res"},{"key":"78786_CR31","doi-asserted-by":"publisher","first-page":"31613","DOI":"10.18632\/oncotarget.5148","volume":"6","author":"M D\u00edaz-Bey\u00e1","year":"2015","unstructured":"D\u00edaz-Bey\u00e1, M. et al. The lincRNA HOTAIRM1, located in the HOXA genomic region, is expressed in acute myeloid leukemia, impacts prognosis in patients in the intermediate-risk cytogenetic category, and is associated with a distinctive microRNA signature. Oncotarget 6, 31613\u201331627. https:\/\/doi.org\/10.18632\/oncotarget.5148 (2015).","journal-title":"Oncotarget"},{"key":"78786_CR32","doi-asserted-by":"publisher","first-page":"S160","DOI":"10.21037\/tcr.2017.02.37","volume":"6","author":"BR Achyut","year":"2017","unstructured":"Achyut, B. R. & Arbab, A. S. Taming immune suppressor: application of myeloid-derived suppressor cells in anti-cancer gene therapy. Transl Cancer Res 6, S160\u2013S162. https:\/\/doi.org\/10.21037\/tcr.2017.02.37 (2017).","journal-title":"Transl Cancer Res"},{"key":"78786_CR33","doi-asserted-by":"publisher","first-page":"e168","DOI":"10.1097\/HS9.0000000000000168","volume":"3","author":"N Bizymi","year":"2019","unstructured":"Bizymi, N. et al. Myeloid-derived suppressor cells in hematologic diseases: promising biomarkers and treatment targets. Hemasphere 3, e168. https:\/\/doi.org\/10.1097\/HS9.0000000000000168 (2019).","journal-title":"Hemasphere"},{"key":"78786_CR34","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.3389\/fimmu.2019.01099","volume":"10","author":"G Pawelec","year":"2019","unstructured":"Pawelec, G., Verschoor, C. P. & Ostrand-Rosenberg, S. Myeloid-derived suppressor cells: Not only in tumor immunity. Front Immunol 10, 1099. https:\/\/doi.org\/10.3389\/fimmu.2019.01099 (2019).","journal-title":"Front Immunol"},{"key":"78786_CR35","doi-asserted-by":"publisher","first-page":"2549","DOI":"10.1182\/blood-2004-07-2521","volume":"105","author":"M Munder","year":"2005","unstructured":"Munder, M. et al. Arginase I is constitutively expressed in human granulocytes and participates in fungicidal activity. Blood 105, 2549\u20132556. https:\/\/doi.org\/10.1182\/blood-2004-07-2521 (2005).","journal-title":"Blood"},{"key":"78786_CR36","doi-asserted-by":"publisher","first-page":"2499","DOI":"10.3389\/fimmu.2018.02499","volume":"9","author":"K Ohl","year":"2018","unstructured":"Ohl, K. & Tenbrock, K. Reactive oxygen species as regulators of MDSC-mediated immune suppression. Front Immunol 9, 2499. https:\/\/doi.org\/10.3389\/fimmu.2018.02499 (2018).","journal-title":"Front Immunol"},{"key":"78786_CR37","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1186\/s13045-016-0333-7","volume":"9","author":"X Tian","year":"2016","unstructured":"Tian, X., Tian, J., Tang, X., Ma, J. & Wang, S. Long non-coding RNAs in the regulation of myeloid cells. J Hematol Oncol 9, 99. https:\/\/doi.org\/10.1186\/s13045-016-0333-7 (2016).","journal-title":"J Hematol Oncol"},{"key":"78786_CR38","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/bs.ctdb.2016.01.006","volume":"118","author":"M Jeong","year":"2016","unstructured":"Jeong, M. & Goodell, M. A. Noncoding Regulatory RNAs in Hematopoiesis. Curr Top Dev Biol 118, 245\u2013270. https:\/\/doi.org\/10.1016\/bs.ctdb.2016.01.006 (2016).","journal-title":"Curr Top Dev Biol"},{"key":"78786_CR39","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1177\/1753425913489850","volume":"20","author":"M El Gazzar","year":"2014","unstructured":"El Gazzar, M. microRNAs as potential regulators of myeloid-derived suppressor cell expansion. Innate Immun 20, 227\u2013238. https:\/\/doi.org\/10.1177\/1753425913489850 (2014).","journal-title":"Innate Immun"},{"key":"78786_CR40","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1053\/j.gastro.2013.07.001","volume":"145","author":"G Koukos","year":"2013","unstructured":"Koukos, G. et al. MicroRNA-124 regulates STAT3 expression and is down-regulated in colon tissues of pediatric patients with ulcerative colitis. Gastroenterology 145, 842-852.e842. https:\/\/doi.org\/10.1053\/j.gastro.2013.07.001 (2013).","journal-title":"Gastroenterology"},{"key":"78786_CR41","doi-asserted-by":"publisher","first-page":"e70300","DOI":"10.1371\/journal.pone.0070300","volume":"8","author":"J Zhang","year":"2013","unstructured":"Zhang, J. et al. MiR-124 suppresses growth of human colorectal cancer by inhibiting STAT3. PLoS ONE 8, e70300. https:\/\/doi.org\/10.1371\/journal.pone.0070300 (2013).","journal-title":"PLoS ONE"},{"key":"78786_CR42","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1084\/jem.20090831","volume":"207","author":"YC Han","year":"2010","unstructured":"Han, Y. C. et al. microRNA-29a induces aberrant self-renewal capacity in hematopoietic progenitors, biased myeloid development, and acute myeloid leukemia. J Exp Med 207, 475\u2013489. https:\/\/doi.org\/10.1084\/jem.20090831 (2010).","journal-title":"J Exp Med"},{"key":"78786_CR43","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1002\/hep.27634","volume":"61","author":"GY Li","year":"2015","unstructured":"Li, G. Y. et al. Hepatitis C virus-induced reduction in miR-181a impairs CD4(+) T-cell responses through overexpression of DUSP6. Hepatology 61, 1163\u20131173. https:\/\/doi.org\/10.1002\/hep.27634 (2015).","journal-title":"Hepatology"},{"key":"78786_CR44","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1111\/imm.12463","volume":"145","author":"YQ Cheng","year":"2015","unstructured":"Cheng, Y. Q. et al. MicroRNA-155 regulates interferon-\u03b3 production in natural killer cells via Tim-3 signalling in chronic hepatitis C virus infection. Immunology 145, 485\u2013497. https:\/\/doi.org\/10.1111\/imm.12463 (2015).","journal-title":"Immunology"},{"key":"78786_CR45","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.imlet.2006.09.005","volume":"107","author":"S Keller","year":"2006","unstructured":"Keller, S., Sanderson, M. P., Stoeck, A. & Altevogt, P. Exosomes: from biogenesis and secretion to biological function. Immunol Lett 107, 102\u2013108. https:\/\/doi.org\/10.1016\/j.imlet.2006.09.005 (2006).","journal-title":"Immunol Lett"},{"key":"78786_CR46","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1146\/annurev-cellbio-101512-122326","volume":"30","author":"M Colombo","year":"2014","unstructured":"Colombo, M., Raposo, G. & Th\u00e9ry, C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol 30, 255\u2013289. https:\/\/doi.org\/10.1146\/annurev-cellbio-101512-122326 (2014).","journal-title":"Annu Rev Cell Dev Biol"},{"key":"78786_CR47","doi-asserted-by":"publisher","first-page":"6328","DOI":"10.1073\/pnas.0914843107","volume":"107","author":"DM Pegtel","year":"2010","unstructured":"Pegtel, D. M. et al. Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci U S A 107, 6328\u20136333. https:\/\/doi.org\/10.1073\/pnas.0914843107 (2010).","journal-title":"Proc Natl Acad Sci U S A"},{"key":"78786_CR48","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1038\/ncb1596","volume":"9","author":"H Valadi","year":"2007","unstructured":"Valadi, H. et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9, 654\u2013659. https:\/\/doi.org\/10.1038\/ncb1596 (2007).","journal-title":"Nat Cell Biol"},{"key":"78786_CR49","doi-asserted-by":"publisher","first-page":"2834","DOI":"10.1002\/eji.200424887","volume":"34","author":"F Masciopinto","year":"2004","unstructured":"Masciopinto, F. et al. Association of hepatitis C virus envelope proteins with exosomes. Eur J Immunol 34, 2834\u20132842. https:\/\/doi.org\/10.1002\/eji.200424887 (2004).","journal-title":"Eur J Immunol"},{"key":"78786_CR50","doi-asserted-by":"publisher","first-page":"e1004424","DOI":"10.1371\/journal.ppat.1004424","volume":"10","author":"TN Bukong","year":"2014","unstructured":"Bukong, T. N., Momen-Heravi, F., Kodys, K., Bala, S. & Szabo, G. Exosomes from hepatitis C infected patients transmit HCV infection and contain replication competent viral RNA in complex with Ago2-miR122-HSP90. PLoS Pathog 10, e1004424. https:\/\/doi.org\/10.1371\/journal.ppat.1004424 (2014).","journal-title":"PLoS Pathog"},{"key":"78786_CR51","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1016\/j.jhep.2013.10.015","volume":"60","author":"FL Cosset","year":"2014","unstructured":"Cosset, F. L. & Dreux, M. HCV transmission by hepatic exosomes establishes a productive infection. J Hepatol 60, 674\u2013675. https:\/\/doi.org\/10.1016\/j.jhep.2013.10.015 (2014).","journal-title":"J Hepatol"},{"key":"78786_CR52","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1016\/j.chom.2012.08.010","volume":"12","author":"M Dreux","year":"2012","unstructured":"Dreux, M. et al. Short-range exosomal transfer of viral RNA from infected cells to plasmacytoid dendritic cells triggers innate immunity. Cell Host Microbe 12, 558\u2013570. https:\/\/doi.org\/10.1016\/j.chom.2012.08.010 (2012).","journal-title":"Cell Host Microbe"},{"key":"78786_CR53","doi-asserted-by":"publisher","first-page":"475","DOI":"10.2217\/fon.13.195","volume":"10","author":"E De Braekeleer","year":"2014","unstructured":"De Braekeleer, E. et al. Hox gene dysregulation in acute myeloid leukemia. Future Oncol 10, 475\u2013495. https:\/\/doi.org\/10.2217\/fon.13.195 (2014).","journal-title":"Future Oncol"},{"key":"78786_CR54","doi-asserted-by":"publisher","first-page":"3645","DOI":"10.1182\/blood-2011-04-346643","volume":"118","author":"IH Hollink","year":"2011","unstructured":"Hollink, I. H. et al. NUP98\/NSD1 characterizes a novel poor prognostic group in acute myeloid leukemia with a distinct HOX gene expression pattern. Blood 118, 3645\u20133656. https:\/\/doi.org\/10.1182\/blood-2011-04-346643 (2011).","journal-title":"Blood"},{"key":"78786_CR55","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1200\/JCO.2009.25.1496","volume":"28","author":"H Becker","year":"2010","unstructured":"Becker, H. et al. Favorable prognostic impact of NPM1 mutations in older patients with cytogenetically normal de novo acute myeloid leukemia and associated gene- and microRNA-expression signatures: a Cancer and Leukemia Group B study. J Clin Oncol 28, 596\u2013604. https:\/\/doi.org\/10.1200\/JCO.2009.25.1496 (2010).","journal-title":"J Clin Oncol"},{"key":"78786_CR56","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.cell.2013.06.020","volume":"154","author":"I Ulitsky","year":"2013","unstructured":"Ulitsky, I. & Bartel, D. P. lincRNAs: Genomics, evolution, and mechanisms. Cell 154, 26\u201346. https:\/\/doi.org\/10.1016\/j.cell.2013.06.020 (2013).","journal-title":"Cell"},{"key":"78786_CR57","first-page":"50","volume":"12","author":"C Liu","year":"2019","unstructured":"Liu, C., Shang, Z., Ma, Y., Ma, J. & Song, J. HOTAIR\/miR-214-3p\/FLOT1 axis plays an essential role in the proliferation, migration, and invasion of hepatocellular carcinoma. Int J Clin Exp Pathol 12, 50\u201363 (2019).","journal-title":"Int J Clin Exp Pathol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-78786-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-78786-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-78786-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T01:00:28Z","timestamp":1670374828000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-78786-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,16]]},"references-count":57,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["78786"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-78786-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,16]]},"assertion":[{"value":"15 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 November 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 December 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"22033"}}