The Role of MicroRNA in Graft-Versus-Host-Disease: A Review

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a clinically challenging modality for the treatment of many hematologic diseases such as leukemia, lymphoma, and myeloma. Graft-versus-host disease (GVHD) is a common complication after allo-HSCT and remains a major cause of morbidity and mortality, limiting the success of a potentially curative transplant. Several microRNAs (miRNAs) have recently been shown to impact the biology of GVHD. They are molecular regulators involved in numerous processes during T-cell development, homeostasis, and activation, and contribute to the pathological function of T-cells during GvHD. Here, we review the key role of miRNAs contributing to the GvHD; their detection might be an interesting possibility in the early diagnosis and monitoring of disease.

Keywords: GVHD; miRNAs; stem cell transplantation.

Figure 1

miRNA maturation. The primary transcript of miRNA (pri-miRNA) is processed by the endoribonuclease DROSHA. The consequently generated precursor miRNAs (pre-miRNAs) are transported from the nucleus to the cytoplasm and cut into 24 bp fragments by the DICER enzyme. After the double-stranded miRNA:miRNA* fragment is loaded into the RNA-induced silencing complex (RISC), the miRNA* is degraded. The RISC complex containing the mature miRNA binds to a target mRNA to inhibit translation by repression of translation or degradation of the mRNA [55].

Figure 2

Schematic representative mechanism of action of the miRNAs studied in this review. Inspired by Sevcikova’s group [61]. The works studied in this review have highlighted that the miRNAs involved in aGVHD (green box) and cGVHD (red box) could be the biomarkers involving the NF-kB, INF- α/γ, and TNF-α pathways, which increase the levels of oxidative stress and cause apoptosis of cells in the target organs of aGVHD, and some of cGVHD.