Integrative Analysis of Long Noncoding RNAs in Patients with Graft-versus-Host Disease
| Autor: | Li Wang, Zhenyang Gu, Chun-Ji Gao, Nan Yang, Feiyan Wang, Lan Luo |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
B-Lymphocytes Microarray analysis techniques breakpoint cluster region Graft vs Host Disease Hematology General Medicine Middle Aged BCR Signaling Pathway Biology Long non-coding RNA 03 medical and health sciences 0302 clinical medicine Gene Expression Regulation hemic and lymphatic diseases 030220 oncology & carcinogenesis Cancer research Humans Female RNA Long Noncoding DNA microarray KEGG Gene B cell receptor signaling pathway 030215 immunology |
| Zdroj: | Acta Haematologica. 143:533-551 |
| ISSN: | 1421-9662 0001-5792 |
| Popis: | Background: Chronic graft-versus-host disease (cGVHD) remains a major cause of late non-recurrence mortality despite remarkable improvements in the field of allogeneic hematopoietic stem cell transplantation. Although recent studies have found that B-cell receptor (BCR)-activated B cells contribute to pathogenesis in cGVHD, the specific molecular mechanisms of B cells in this process remain unclear. Methods: In our study, human long noncoding RNA (lncRNA) microarrays and bioinformatic analysis were performed to identify different expressions of lncRNAs in peripheral blood B cells from cGVHD patients compared with healthy ones. The differential expression of lncRNA was confirmed in additional samples by quantitative real-time polymerase chain reaction (qRT-PCR). Results: The microarray analysis revealed that 106 of 198 differentially expressed lncRNAs were upregulated and 92 were downregulated in cGVHD patients compared with healthy controls. Intergenic lncRNAs accounted for the majority of differentially expressed lncRNAs. A KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis showed that the differentially expressed mRNAs, which were coexpressed with lncRNA, between the cGVHD group and the healthy group were significantly enriched in the BCR signaling pathway. Further analysis of the BCR signaling pathway and its coexpression network identified three lncRNAs with the strongest correlation with BCR signaling and cGVHD, as well as a series of protein-coding genes and transcription factors associated with them. The three candidate lncRNAs were further validated in another group of cGVHD patients by qRT-PCR. Conclusions: This is the first study on the correlation between lncRNA and cGVHD using lncRNA microarray analysis. Our study provides novel enlightenment in exploring the molecular pathogenesis of cGVHD. |
| Databáze: | OpenAIRE |
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