{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:13:21Z","timestamp":1790018001903,"version":"4.0.1"},"reference-count":78,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T00:00:00Z","timestamp":1608249600000},"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, R21AI138598, and S10OD021572"],"award-info":[{"award-number":["R01AI114748, R21AI138598, and S10OD021572"]}],"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 and 1I01BX004281"],"award-info":[{"award-number":["1I01BX002670 and 1I01BX004281"]}],"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":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>RUNX1 overlapping RNA (RUNXOR) is a long non-coding RNA and plays a pivotal role in the differentiation of myeloid cells via targeting runt-related transcription factor 1 (RUNX1). We and others have previously reported that myeloid-derived suppressor cells (MDSCs) expand and inhibit host immune responses during chronic viral infections; however, the mechanisms responsible for MDSC differentiation and suppressive functions, in particular the role of RUNXOR\u2013RUNX1, remain unclear. Here, we demonstrated that RUNXOR and RUNX1 expressions are significantly upregulated and associated with elevated levels of immunosuppressive molecules, such as arginase 1 (Arg1), inducible nitric oxide synthase (iNOS), signal transducer and activator of transcription 3 (STAT3), and reactive oxygen species (ROS) in MDSCs during chronic hepatitis C virus (HCV) infection. Mechanistically, we discovered that HCV-associated exosomes (HCV-Exo) can induce the expressions of RUNXOR and RUNX1, which in turn regulates miR-124 expression via STAT3 signaling, thereby promoting MDSC differentiation and suppressive functions. Importantly, overexpression of RUNXOR in healthy CD33+ myeloid cells promoted differentiation and suppressive functions of MDSCs. Conversely, silencing RUNXOR or RUNX1 expression in HCV-derived CD33+ myeloid cells significantly inhibited their differentiation and expressions of suppressive molecules and improved the function of co-cultured autologous CD4 T cells. Taken together, these results indicate that the RUNXOR\u2013RUNX1\u2013STAT3\u2013miR124 axis enhances the differentiation and suppressive functions of MDSCs and could be a potential target for immunomodulation in conjunction with antiviral therapy during chronic HCV infection.<\/jats:p>","DOI":"10.3390\/cells9122715","type":"journal-article","created":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T04:12:01Z","timestamp":1608523921000},"page":"2715","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["HCV-Associated Exosomes Upregulate RUNXOR and RUNX1 Expressions to Promote MDSC Expansion and Suppressive Functions through STAT3\u2013miR124 Axis"],"prefix":"10.3390","volume":"9","author":[{"given":"Bal Krishna Chand","family":"Thakuri","sequence":"first","affiliation":[{"name":"Center of Excellence for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA"},{"name":"Division of Infectious, Inflammatory and Immunologic Diseases, Department of Internal Medicine, Quillen College of Medicine, ETSU, Johnson City, TN 37614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center of Excellence for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA"},{"name":"Division of Infectious, Inflammatory and Immunologic Diseases, Department of Internal Medicine, Quillen College of Medicine, ETSU, Johnson City, TN 37614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Center of Excellence for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA"},{"name":"Division of Infectious, Inflammatory and Immunologic Diseases, Department of Internal Medicine, Quillen College of Medicine, ETSU, Johnson City, TN 37614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lam N.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Center of Excellence for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA"},{"name":"Division of Infectious, Inflammatory and Immunologic Diseases, Department of Internal Medicine, Quillen College of Medicine, ETSU, Johnson City, TN 37614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lam N. T.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Center of Excellence for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA"},{"name":"Division of Infectious, Inflammatory and Immunologic Diseases, Department of Internal Medicine, Quillen College of Medicine, ETSU, Johnson City, TN 37614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison","family":"Schank","sequence":"additional","affiliation":[{"name":"Center of Excellence for Inflammation, Infectious Disease and Immunity, James H. 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Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA"},{"name":"Division of Infectious, Inflammatory and Immunologic Diseases, Department of Internal Medicine, Quillen College of Medicine, ETSU, Johnson City, TN 37614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xindi","family":"Dang","sequence":"additional","affiliation":[{"name":"Center of Excellence for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA"},{"name":"Division of Infectious, Inflammatory and Immunologic Diseases, Department of Internal Medicine, Quillen College of Medicine, ETSU, Johnson City, TN 37614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dechao","family":"Cao","sequence":"additional","affiliation":[{"name":"Center of Excellence for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA"},{"name":"Division of Infectious, Inflammatory and Immunologic Diseases, Department of Internal Medicine, Quillen College of Medicine, ETSU, Johnson City, TN 37614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyuan","family":"Lu","sequence":"additional","affiliation":[{"name":"Center of Excellence for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA"},{"name":"Division of Infectious, Inflammatory and Immunologic Diseases, Department of Internal Medicine, Quillen College of Medicine, ETSU, Johnson City, TN 37614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao Y.","family":"Wu","sequence":"additional","affiliation":[{"name":"Center of Excellence for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA"},{"name":"Division of Infectious, Inflammatory and Immunologic Diseases, Department of Internal Medicine, Quillen College of Medicine, ETSU, Johnson City, TN 37614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Center of Excellence for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"El Gazzar","sequence":"additional","affiliation":[{"name":"Center of Excellence for Inflammation, Infectious Disease and Immunity, James H. 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Quillen VA Medical Center, Department of Veterans Affairs, Johnson City, TN 37614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4121","DOI":"10.1172\/JCI67714","article-title":"Emerging concepts in immunity to hepatitis C virus infection","volume":"123","author":"Rosen","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.immuni.2013.12.010","article-title":"Immune Responses to HCV and Other Hepatitis Viruses","volume":"40","author":"Park","year":"2014","journal-title":"Immunity"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/nrd4050","article-title":"Novel therapies for hepatitis C\u2014One pill fits all?","volume":"12","author":"Manns","year":"2013","journal-title":"Nat. Rev. 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