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

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.

Toll-Like Receptor Stimulation by MicroRNAs in Acute Graft-vs.-Host Disease

“…In contrast to canonical biogenesis of miRs, emerging data supports the findings that miRs can also be stably found in a variety of body fluids, such as saliva ( 70 , 71 ), urine ( 72 ), and blood ( 73 , 74 ) either packaged within exosomes or in complexes with RNA-binding proteins such as Ago or high-density lipoprotein. These miRs, referred to as cell-free miRs ( 75 ), may serve as biomarkers of disease ( 71 , 72 , 74 ) and/or facilitators of disease pathogenesis through cell-to-cell communication ( 75 – 78 ).…”

The Role of MicroRNAs in Myeloid Cells during Graft-versus-Host Disease

“…In mouse models, GvHD biology was functionally linked to several miRs, e.g., miR-155 ( 14 , 15 ), miR-100 ( 16 ), miR-146a ( 17 , 18 ), miR-142 ( 19 ), miR-17-92 ( 20 ), miR-153-3p ( 21 ), and miR-29a ( 22 ).…”

“…There is increasing evidence that serum or plasma miRs could be used as biomarkers and predict acute GvHD onset ( 23 ). A study suggested miR-153-3p as a potential biomarker for GvHD because miR-153-3p plasma levels were elevated on day seven after allo-HCT in the GvHD group compared to the control group even though GvHD had not occurred yet ( 21 ). Through bioinformatics analysis, indoleamine 2,3-dioxygenase (IDO) was found to be a potential target protein of miR-153-3p ( 21 ).…”

“…A study suggested miR-153-3p as a potential biomarker for GvHD because miR-153-3p plasma levels were elevated on day seven after allo-HCT in the GvHD group compared to the control group even though GvHD had not occurred yet ( 21 ). Through bioinformatics analysis, indoleamine 2,3-dioxygenase (IDO) was found to be a potential target protein of miR-153-3p ( 21 ). The authors hypothesized that IDO might inhibit the development of acute GvHD through various cell types in addition to lymphocytes, such as DCs and myeloid-derived suppressor cells ( 21 ).…”

“…Through bioinformatics analysis, indoleamine 2,3-dioxygenase (IDO) was found to be a potential target protein of miR-153-3p ( 21 ). The authors hypothesized that IDO might inhibit the development of acute GvHD through various cell types in addition to lymphocytes, such as DCs and myeloid-derived suppressor cells ( 21 ). In a previous study, IDO expression in donor precursors of plasmacytoid DCs had been shown to suppress GvHD activity of donor T cells and to influence their polarization in a murine model ( 24 ).…”