Introduction: Acute graft-versus-host disease (aGVHD) is one of the major complications of allogeneic hematopoietic stem cell transplantation, and the liver, skin, and gastrointestinal tract are the main target organs. The most common type is intestinal aGVHD. Long noncoding RNAs (lncRNAs) have coregulatory functions and participate in a variety of intracellular regulatory processes. We investigated the expression of lncRNAs and their mechanisms in the development of aGVHD.
Methods: The participants included 15 patients with aGVHD and 4 healthy controls (HCs). To generate profiles of abnormally expressed lncRNAs, peripheral blood mononuclear cell (PBMC) lncRNAs from four patients and four HCs were validated by high-throughput sequencing and quantitative real-time-PCR (qRT-PCR). A number of databases, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, miRanda, TargetScan, and Metascape, were used for bioinformatics analysis. Bioinformatics analysis indicated that overexpression of lnc-AC145676.2.1-6-3 might induce aGVHD via the interleukin (IL)-1β axis and a downstream miRNA. After the higher levels of lnc-AC145676.2.1-6-3 in other patients were confirmed by qRT-PCR, serum IL-1β, IL-6, and tumor necrosis factor-α were measured by enzyme linked immunosorbent assays.
Results: In our study, a large number of lncRNAs were found in PBMCs of patients with intestinal aGVHD, and bioinformatics analysis showed that the upregulated lncRNA lnc-AC145676.2.1-6-3 probably affected the progression of intestinal aGVHD by regulating the hsa-miR-3064-5p/IL-1β axis. In addition, the changes in lncRNA expression levels were positively correlated with the clinical characteristics of intestinal aGVHD.
Conclusion: Our results suggest that lncRNAs in PBMCs may become new biomarkers and therapeutic targets for intestinal aGVHD.
Keywords: IL-1β; intestinal acute graft versus host disease; lncRNAs; sequencing.
© 2022 John Wiley & Sons Ltd.