Oncotarget

Research Papers:

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

Xiao-su Zhao _, Yi-nuo Wang, Meng Lv, Yuan Kong, Hong-xue Luo, Xiao-yang Ye, Qi Wu, Tong-feng Zhao, Yue-huan Hu, Hong-yu Zhang, Ming-rui Huo, Jun Wan and Xiao-jun Huang

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Oncotarget. 2016; 7:48321-48334. https://doi.org/10.18632/oncotarget.10220

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Abstract

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

Correspondence to:

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

ABSTRACT

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.


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