Dataset Information

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

ABSTRACT: The successful treatment of various hematologic diseases with allogeneic hematopoietic cell transplantation is often limited by the occurrence of graft-versus-host disease (GvHD). Several microRNAs (miRs) have recently been shown to impact the biology of GvHD by regulating pro- as well as anti-inflammatory target genes. There is increasing evidence that a single miR can have different effects by preferentially targeting certain genes depending on the cell type that the miR is analyzed in. This review will focus on the role of miRs in myeloid cells during the development of acute and chronic GvHD and autoimmune diseases. Because miRs act on the expression of multiple target genes and may thereby influence the immune system at different functional levels, they are potentially attractive targets for the modification of allogeneic immune responses using miR mimics and inhibitors.

SUBMITTER: Chen S

PROVIDER: S-EPMC5787138 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Chen Sophia S Zeiser Robert R

Frontiers in immunology 20180123

The successful treatment of various hematologic diseases with allogeneic hematopoietic cell transplantation is often limited by the occurrence of graft-versus-host disease (GvHD). Several microRNAs (miRs) have recently been shown to impact the biology of GvHD by regulating pro- as well as anti-inflammatory target genes. There is increasing evidence that a single miR can have different effects by preferentially targeting certain genes depending on the cell type that the miR is analyzed in. This r ...[more]

PMID: 29410665

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Project description:Acute graft-versus-host disease (aGvHD) is the most frequent and serious complication following hematopoietic stem cell transplantation (HSCT), with a high mortality rate. A clearer understanding of the molecular pathogenesis may allow for improved therapeutic options or guide personalized prophylactic protocols. Circulating microRNAs are expressed in body fluids and have recently been associated with the etiology of aGvHD, but global expression profiling in a HSCT setting is lacking. This study profiled expression of n = 799 mature microRNAs in patient serum, using the NanoString platform, to identify microRNAs that showed altered expression at aGvHD diagnosis. Selected microRNAs (n = 10) were replicated in independent cohorts of serum samples taken at aGvHD diagnosis (n = 42) and prior to disease onset (day 14 post-HSCT, n = 47) to assess their prognostic potential. Sera from patients without aGvHD were used as controls. Differential microRNAs were investigated in silico for predicted networks and mRNA targets. Expression analysis identified 61 microRNAs that were differentially expressed at aGvHD diagnosis. miR-146a (p = 0.03), miR-30b-5p (p = 0.007), miR-374-5p (p = 0.02), miR-181a (p = 0.03), miR-20a (p = 0.03), and miR-15a (p = 0.03) were significantly verified in an independent cohort (n = 42). miR-146a (p = 0.01), miR-20a (p = 0.03), miR-18 (p = 0.03), miR-19a (p = 0.03), miR-19b (p = 0.01), and miR-451 (p = 0.01) were differentially expressed 14 days post-HSCT in patients who later developed aGvHD (n = 47). High miR-19b expression was associated with improved overall survival (OS) (p = 0.008), whereas high miR-20a and miR-30b-5p were associated with lower rates of non-relapse mortality (p = 0.05 and p = 0.008) and improved OS (p = 0.016 and p = 0.021). Pathway analysis associated the candidate microRNAs with hematological and inflammatory disease. Circulating biofluid microRNAs show altered expression at aGvHD onset and have the capacity to act as prognostic and diagnostic biomarkers. Their differential expression in serum suggests a role for circulatory microRNAs in aGvHD pathology, which warrants further investigation.

Dataset Information

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

Publications

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

Similar Datasets

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