miR-153-3p, a new bio-target, is involved in the pathogenesis of acute graft-versus-host disease via inhibition of indoleamine- 2,3-dioxygenase
Metrics: PDF 2011 views | HTML 1875 views | ?
Xiao-su Zhao1,6,*, Yi-nuo Wang2,*, Meng Lv1, Yuan Kong1,6, Hong-xue Luo2, Xiao-yang Ye2, Qi Wu2, Tong-feng Zhao2, Yue-huan Hu2, Hong-yu Zhang4, Ming-Rui Huo1, Jun Wan2,5, Xiao-jun Huang1,3,6
1Peking University People’s Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
2Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, Shenzhen, China
3Peking-Tsinghua Center for Life Sciences, Beijing, China
4Department of Hematology, Peking University Shenzhen Hospital, Shenzhen, China
5Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China
6Collaborative Innovation Center of Hematology, Peking University, Beijing, China
*These authors have contributed equally to this work
Xiao-jun Huang, email: [email protected]
Jun-Wan, email: [email protected]
Keywords: acute graft-versus-host disease, microRNA, allogeneic hematopoietic stem cell transplantation, indoleamine-2,3-dioxygenase, regulation
Received: December 20, 2015 Accepted: June 09, 2016 Published: June 22, 2016
Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Therefore, seeking reliable biomarkers and delineating the potential biological mechanism are important for optimizing treatment strategies and improving their curative effect. In this study, using a microRNA polymerase chain reaction (PCR)-based chip assay, microRNA-153-3p (miR-153-3p) was screened and selected as a potential biomarker of aGVHD. The elevated plasma miR-153-3p levels at +7 d after transplant could be used to predict the upcoming aGVHD. The area under the receiver operating characteristic curve for aGVHD+/aGVHD- patients receiving haploidentical transplant was 0.808 (95% confidence interval, 0.686-0.930) in a training set and 0.809 (95% confidence interval, 0.694-0.923) in a validation set. Interestingly, bioinformatics analysis indicated that indoleamine-2,3-dioxygenase (IDO) is a potential target of miR-153-3p. In vitro study confirmed that IDO could be directly inhibited by miR-153-3p. In a GVHD model, recipient mice injected with a miR-153-3p antagomir exhibited higher IDO expression levels at the early stage after transplantation, as well as delayed aGVHD and longer survival, indicating that the miR-153-3p level at +7 d post-transplant is a good predictor of aGVHD. miR-153-3p participates in aGVHD development by inhibiting IDO expression and might be a novel bio-target for aGVHD intervention.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.