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Volume 19
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10.3390/ijms19092493
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Article

Exosomal miRNA Signatures for Late-Onset Acute Graft-Versus-Host Disease in Allogenic Hematopoietic Stem Cell Transplantation

by
Seiichiro Yoshizawa
1,*,
Tomohiro Umezu
1,2,
Yuu Saitoh
1,
Moritaka Gotoh
1,
Daigo Akahane
1,
Chiaki Kobayashi
1,
Junko H. Ohyashiki
2 and
Kazuma Ohyashiki
1,2
1
Department of Hematology, Tokyo Medical University, Tokyo 160-0023, Japan
2
Department of Advanced Cellular Therapy, Tokyo Medical University, Tokyo 160-0023, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(9), 2493; https://doi.org/10.3390/ijms19092493
Submission received: 27 July 2018 / Revised: 15 August 2018 / Accepted: 21 August 2018 / Published: 23 August 2018
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Abstract

Recent studies have demonstrated that exosomal microRNAs (miRNAs) have the potential of facilitating molecular diagnosis. Currently, little is known about the underlying mechanism behind late-onset acute graft-versus-host disease (LA GVHD). Identifying differentially expressed miRNAs in exosomes should be useful for understanding the role of miRNAs in this disease. This study was established to investigate the relevance of miRNAs in exosomes derived from patients developing LA GVHD after allogeneic hematopoietic stem cell transplantation (HSCT). Plasma samples were collected from patients with LA GVHD (n = 5), non-GVHD (n = 5), and controls (n = 8) for exosomal miRNA expression profiling using a TaqMan low-density array; the results were validated by quantitative reverse transcription polymerase chain reaction (RT-PCR). We analyzed exosomal miRNAs differentially expressed among these three groups. MirTarBase was employed to predict potential target genes of the miRNAs specific for LA GVHD. We detected 55 miRNAs that were differentially expressed with a significant change >2.0-fold between LA GVHD and non-GVHD. Of these, we selected the 10 miRNAs (miR-423-5p, miR-19a, miR-142-3p, miR-128, miR-193b, miR-30c, miR-193a, miR-191, miR-125b, and miR-574-3p) with the most significant differential expression. Using quantitative RT-PCR, we further identified that miR-128 was significantly upregulated at the onset of LA GVHD compared with that in normal controls and is a promising diagnostic marker of LA GVHD, with an area under the curve (AUC) value of 0.975. MirTarBase analysis revealed that the predicted target genes of miR-128 are involved in the immune system and inflammation. Increased expression of miR-128 may serve as a novel, noninvasive biomarker for early LA GVHD diagnosis.
Keywords: late-onset acute graft-versus-host disease; exosomal miRNA; hematopoietic stem cell transplantation late-onset acute graft-versus-host disease; exosomal miRNA; hematopoietic stem cell transplantation
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MDPI and ACS Style

Yoshizawa, S.; Umezu, T.; Saitoh, Y.; Gotoh, M.; Akahane, D.; Kobayashi, C.; Ohyashiki, J.H.; Ohyashiki, K. Exosomal miRNA Signatures for Late-Onset Acute Graft-Versus-Host Disease in Allogenic Hematopoietic Stem Cell Transplantation. Int. J. Mol. Sci. 2018, 19, 2493. https://doi.org/10.3390/ijms19092493

AMA Style

Yoshizawa S, Umezu T, Saitoh Y, Gotoh M, Akahane D, Kobayashi C, Ohyashiki JH, Ohyashiki K. Exosomal miRNA Signatures for Late-Onset Acute Graft-Versus-Host Disease in Allogenic Hematopoietic Stem Cell Transplantation. International Journal of Molecular Sciences. 2018; 19(9):2493. https://doi.org/10.3390/ijms19092493

Chicago/Turabian Style

Yoshizawa, Seiichiro, Tomohiro Umezu, Yuu Saitoh, Moritaka Gotoh, Daigo Akahane, Chiaki Kobayashi, Junko H. Ohyashiki, and Kazuma Ohyashiki. 2018. "Exosomal miRNA Signatures for Late-Onset Acute Graft-Versus-Host Disease in Allogenic Hematopoietic Stem Cell Transplantation" International Journal of Molecular Sciences 19, no. 9: 2493. https://doi.org/10.3390/ijms19092493

APA Style

Yoshizawa, S., Umezu, T., Saitoh, Y., Gotoh, M., Akahane, D., Kobayashi, C., Ohyashiki, J. H., & Ohyashiki, K. (2018). Exosomal miRNA Signatures for Late-Onset Acute Graft-Versus-Host Disease in Allogenic Hematopoietic Stem Cell Transplantation. International Journal of Molecular Sciences, 19(9), 2493. https://doi.org/10.3390/ijms19092493

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