tRNA 及其衍生的小 RNA 在系统性红斑狼疮发生发展中的潜在作用。

The potential role of tRNAs and small RNAs derived from tRNAs in the occurrence and development of systemic lupus erythematosus.

机构信息

Department of Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital Southern University of Science and Technology, Shenzhen People's Hospital, Shenzhen, Guangdong, 518020, People's Republic of China.

出版信息

Biochem Biophys Res Commun. 2020 Jun 25;527(2):561-567. doi: 10.1016/j.bbrc.2020.04.114. Epub 2020 May 15.

DOI:10.1016/j.bbrc.2020.04.114

PMID:32423797

Abstract

BACKGROUND

Emerging evidence has shown the involvement of dysregulated transfer RNAs (tRNAs) and small RNAs derived from transfer RNAs (tsRNAs) in the pathophysiology of human diseases. The role of tRNAs and tsRNAs in systemic lupus erythematosus (SLE) remains unclear. Therefore, this study aims to investigate the possible regulatory roles of tRNAs and tsRNAs in the pathological mechanism of SLE.

METHODS

Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of 20 SLE patients and 20 normal controls (NCs) to obtain tRNAs and tsRNAs, followed by tRNA and tsRNA expression profiling by the NextSeq system. Target genes were predicted by informatics analysis. Subsequently, to explore the function of messenger RNA (mRNA) in these target genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the Cytoscape plug-in BinGo, the DAVID database, and Cytoscape software.

RESULTS

A total of 101 tRNAs and 355 tsRNAs were found to be differentially expressed in SLE patients versus NCs by RNA microarray. GO analysis revealed that the altered target genes of the selected tRNAs and tsRNAs were most enriched similarly in immune response and the immune system process. Moreover, KEGG pathway analysis demonstrated that altered target genes of tRNAs were most enriched in systemic lupus erythematosus, while the altered target genes of tsRNAs were most enriched in the T cell receptor signalling pathway, Th1 and Th2 cell differentiation and primary immunodeficiency. These pathways may be related to the initiation of SLE.

CONCLUSION

Our results provide a novel perspective for studying the tRNA-related and tsRNA-related pathogenesis of SLE.

摘要

背景

新出现的证据表明，失调的转移 RNA（tRNA）和来自转移 RNA 的小 RNA（tsRNA）参与了人类疾病的病理生理学。tRNA 和 tsRNA 在系统性红斑狼疮（SLE）中的作用尚不清楚。因此，本研究旨在探讨 tRNA 和 tsRNA 在 SLE 病理机制中的可能调节作用。

方法

从 20 例系统性红斑狼疮患者和 20 例正常对照者（NCs）的外周血单个核细胞（PBMCs）中提取总 RNA，获得 tRNA 和 tsRNA，然后通过 NextSeq 系统进行 tRNA 和 tsRNA 表达谱分析。通过信息学分析预测靶基因。随后，为了探讨这些靶基因中信使 RNA（mRNA）的功能，使用 Cytoscape 插件 BinGo、DAVID 数据库和 Cytoscape 软件对基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路进行分析。

结果

通过 RNA 微阵列发现，SLE 患者与 NCs 相比，共有 101 种 tRNA 和 355 种 tsRNA 表达差异。GO 分析表明，所选 tRNA 和 tsRNA 的改变靶基因在免疫反应和免疫系统过程中富集程度相似。此外，KEGG 通路分析表明，tRNA 改变靶基因在系统性红斑狼疮中最为丰富，而 tsRNA 改变靶基因在 T 细胞受体信号通路、Th1 和 Th2 细胞分化以及原发性免疫缺陷中最为丰富。这些途径可能与 SLE 的发生有关。