MicroRNA‐181a, a potential diagnosis marker, alleviates acute graft versus host disease by regulating IFN‐γ production
Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is a valuable therapeutic strategy for a wide variety of diseases. Acute graft‐versus‐host disease (aGVHD) is a major complication in up to 75% of allo‐HSCT. The absence of a reliable predicative marker for aGVHD onset prevents preemptiv...
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| Published in | American journal of hematology Vol. 90; no. 11; pp. 998 - 1007 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
01.11.2015
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| Abstract | Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is a valuable therapeutic strategy for a wide variety of diseases. Acute graft‐versus‐host disease (aGVHD) is a major complication in up to 75% of allo‐HSCT. The absence of a reliable predicative marker for aGVHD onset prevents preemptive treatment and impedes widespread and successful application of this therapy. In this study we found that after allo‐HSCT, the levels of miR‐181a were reduced significantly prior to the onset of aGVHD. More importantly, the degree of its reduction correlated with the severity of aGVHD. Mechanistically, miR‐181a affects the function of T lymphocytes by down‐regulating IFN‐γ in a dose‐dependent manner. Meanwhile, we confirmed that miR‐181a can effectively preserve the anti‐leukemic effect in vitro. Using a murine allo‐HSCT model, we demonstrated that murine miR‐181b, the human miR‐181a homolog, served as an effective predictor of aGVHD. Moreover, expression of this microRNA ameliorated the severity of aGVHD. Collectively, these results show that the level of miR‐181a may serve as a reliable marker for the diagnosis and prognosis the onset of aGVHD. Am. J. Hematol. 90:998–1007, 2015. © 2015 Wiley Periodicals, Inc. |
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| AbstractList | Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a valuable therapeutic strategy for a wide variety of diseases. Acute graft-versus-host disease (aGVHD) is a major complication in up to 75% of allo-HSCT. The absence of a reliable predicative marker for aGVHD onset prevents preemptive treatment and impedes widespread and successful application of this therapy. In this study we found that after allo-HSCT, the levels of miR-181a were reduced significantly prior to the onset of aGVHD. More importantly, the degree of its reduction correlated with the severity of aGVHD. Mechanistically, miR-181a affects the function of T lymphocytes by down-regulating IFN-γ in a dose-dependent manner. Meanwhile, we confirmed that miR-181a can effectively preserve the anti-leukemic effect in vitro. Using a murine allo-HSCT model, we demonstrated that murine miR-181b, the human miR-181a homolog, served as an effective predictor of aGVHD. Moreover, expression of this microRNA ameliorated the severity of aGVHD. Collectively, these results show that the level of miR-181a may serve as a reliable marker for the diagnosis and prognosis the onset of aGVHD. Am. J. Hematol. 90:998-1007, 2015. © 2015 Wiley Periodicals, Inc. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a valuable therapeutic strategy for a wide variety of diseases. Acute graft-versus-host disease (aGVHD) is a major complication in up to 75% of allo-HSCT. The absence of a reliable predicative marker for aGVHD onset prevents preemptive treatment and impedes widespread and successful application of this therapy. In this study we found that after allo-HSCT, the levels of miR-181a were reduced significantly prior to the onset of aGVHD. More importantly, the degree of its reduction correlated with the severity of aGVHD. Mechanistically, miR-181a affects the function of T lymphocytes by down-regulating IFN-γ in a dose-dependent manner. Meanwhile, we confirmed that miR-181a can effectively preserve the anti-leukemic effect in vitro . Using a murine allo-HSCT model, we demonstrated that murine miR-181b, the human miR-181a homolog, served as an effective predictor of aGVHD. Moreover, expression of this microRNA ameliorated the severity of aGVHD. Collectively, these results show that the level of miR-181a may serve as a reliable marker for the diagnosis and prognosis the onset of aGVHD. Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is a valuable therapeutic strategy for a wide variety of diseases. Acute graft‐versus‐host disease (aGVHD) is a major complication in up to 75% of allo‐HSCT. The absence of a reliable predicative marker for aGVHD onset prevents preemptive treatment and impedes widespread and successful application of this therapy. In this study we found that after allo‐HSCT, the levels of miR‐181a were reduced significantly prior to the onset of aGVHD. More importantly, the degree of its reduction correlated with the severity of aGVHD. Mechanistically, miR‐181a affects the function of T lymphocytes by down‐regulating IFN‐γ in a dose‐dependent manner. Meanwhile, we confirmed that miR‐181a can effectively preserve the anti‐leukemic effect in vitro . Using a murine allo‐HSCT model, we demonstrated that murine miR‐181b, the human miR‐181a homolog, served as an effective predictor of aGVHD. Moreover, expression of this microRNA ameliorated the severity of aGVHD. Collectively, these results show that the level of miR‐181a may serve as a reliable marker for the diagnosis and prognosis the onset of aGVHD. Am. J. Hematol. 90:998–1007, 2015. © 2015 Wiley Periodicals, Inc. |
| Author | Sun, Cai Chen, Chong Yan, Dongmei Zhang, Cong Zhang, Dianzheng Zeng, Lingyu Li, Depeng Wang, Ying Zhu, Feng Zhao, Kai Xu, Kailin Cao, Jiang Sang, Wei Loughran, Thomas P. Zhou, Cui Chen, Wei Li, Zhenyu Sun, Xiaoshen Wu, Qingyun Pan, Bin Niu, Mingshan |
| AuthorAffiliation | 5 Department of Medicine, University of Virginia Cancer Center, Virginia, USA 3 Department of Biochemistry and Molecular Biology, Philadelphia College of Osteopathic Medicine, USA 2 The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China 1 The first clinical medical college of Nanjing Medical University, Nanjing, China 4 Department of Medicine, Penn State Hershey Cancer Institute, Hershey, Pennsylvania, USA |
| AuthorAffiliation_xml | – name: 1 The first clinical medical college of Nanjing Medical University, Nanjing, China – name: 4 Department of Medicine, Penn State Hershey Cancer Institute, Hershey, Pennsylvania, USA – name: 5 Department of Medicine, University of Virginia Cancer Center, Virginia, USA – name: 2 The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China – name: 3 Department of Biochemistry and Molecular Biology, Philadelphia College of Osteopathic Medicine, USA |
| Author_xml | – sequence: 1 givenname: Wei surname: Sang fullname: Sang, Wei organization: Affiliated Hospital of Xuzhou Medical College – sequence: 2 givenname: Cong surname: Zhang fullname: Zhang, Cong organization: Affiliated Hospital of Xuzhou Medical College – sequence: 3 givenname: Dianzheng surname: Zhang fullname: Zhang, Dianzheng organization: Philadelphia College of Osteopathic Medicine – sequence: 4 givenname: Ying surname: Wang fullname: Wang, Ying organization: Affiliated Hospital of Xuzhou Medical College – sequence: 5 givenname: Cai surname: Sun fullname: Sun, Cai organization: Affiliated Hospital of Xuzhou Medical College – sequence: 6 givenname: Mingshan surname: Niu fullname: Niu, Mingshan organization: Affiliated Hospital of Xuzhou Medical College – sequence: 7 givenname: Xiaoshen surname: Sun fullname: Sun, Xiaoshen organization: Penn State Hershey Cancer Institute – sequence: 8 givenname: Cui surname: Zhou fullname: Zhou, Cui organization: Affiliated Hospital of Xuzhou Medical College – sequence: 9 givenname: Lingyu surname: Zeng fullname: Zeng, Lingyu organization: Affiliated Hospital of Xuzhou Medical College – sequence: 10 givenname: Bin surname: Pan fullname: Pan, Bin organization: Affiliated Hospital of Xuzhou Medical College – sequence: 11 givenname: Wei surname: Chen fullname: Chen, Wei organization: Affiliated Hospital of Xuzhou Medical College – sequence: 12 givenname: Dongmei surname: Yan fullname: Yan, Dongmei organization: Affiliated Hospital of Xuzhou Medical College – sequence: 13 givenname: Feng surname: Zhu fullname: Zhu, Feng organization: Affiliated Hospital of Xuzhou Medical College – sequence: 14 givenname: Qingyun surname: Wu fullname: Wu, Qingyun organization: Affiliated Hospital of Xuzhou Medical College – sequence: 15 givenname: Jiang surname: Cao fullname: Cao, Jiang organization: Affiliated Hospital of Xuzhou Medical College – sequence: 16 givenname: Kai surname: Zhao fullname: Zhao, Kai organization: Affiliated Hospital of Xuzhou Medical College – sequence: 17 givenname: Chong surname: Chen fullname: Chen, Chong organization: Affiliated Hospital of Xuzhou Medical College – sequence: 18 givenname: Zhenyu surname: Li fullname: Li, Zhenyu organization: Affiliated Hospital of Xuzhou Medical College – sequence: 19 givenname: Depeng surname: Li fullname: Li, Depeng organization: Affiliated Hospital of Xuzhou Medical College – sequence: 20 givenname: Thomas P. surname: Loughran fullname: Loughran, Thomas P. organization: University of Virginia Cancer Center – sequence: 21 givenname: Kailin surname: Xu fullname: Xu, Kailin organization: Affiliated Hospital of Xuzhou Medical College |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26223969$$D View this record in MEDLINE/PubMed |
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| Notes | T.P.L. and K.X. share senior authorship. Nothing to report. W.S. and C.Z. contributed equally to this work. Conflict of interest ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Thomas P. Loughran Jr and Kailin Xu share senior authorship |
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| Snippet | Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is a valuable therapeutic strategy for a wide variety of diseases. Acute graft‐versus‐host... Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a valuable therapeutic strategy for a wide variety of diseases. Acute graft-versus-host... |
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| SubjectTerms | Acute Disease Adolescent Adult Animals Biomarkers - metabolism Disease Models, Animal Female Gene Expression Regulation Graft vs Host Disease - diagnosis Graft vs Host Disease - genetics Graft vs Host Disease - immunology Graft vs Host Disease - mortality Hematopoietic Stem Cell Transplantation Humans Interferon-gamma - genetics Interferon-gamma - immunology Male Mice, Inbred BALB C Mice, Inbred C57BL MicroRNAs - genetics MicroRNAs - immunology Middle Aged Prognosis Signal Transduction Survival Analysis Transplantation, Homologous Whole-Body Irradiation |
| Title | MicroRNA‐181a, a potential diagnosis marker, alleviates acute graft versus host disease by regulating IFN‐γ production |
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