Analysis of differential expression of long non‑coding RNAs in exosomes derived from mature and immature dendritic cells

对成熟和未成熟树突状细胞来源的外泌体中长链非编码RNA差异表达的分析

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作者:Jiachang Wu # ,Renli Zhao # ,Jingxing Dai ,Guohua Lai ,Asmat Ullah Khan ,Xiao Yu ,Sha Wu ,Jun Ouyang ,Hongxun Sang

Abstract

Dendritic cells release bioactive exosomes involved in immune regulation. Long non‑coding RNAs (lncRNAs) are implicated in a number of immunoregulatory mechanisms. However, the roles of lncRNAs in dendritic cell‑derived exosomes remain to be elucidated. The present study aimed to investigate the roles of lncRNAs in exosomes derived from mature and immature dendritic cells and to find specific lncRNAs with immunoregulatory function. The expression profiles of lncRNAs in exosomes derived from bone marrow dendritic cells of C57 mice were illustrated. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and Gene Set Enrichment Analysis were performed to identify potential targets correlated with immune regulation. In addition, lncRNA‑miRNA‑mRNA networks were predicted using bioinformatics methods. Representative lncRNAs were further validated via reverse transcription‑quantitative PCR. A total of 437 lncRNAs were analyzed using RNA‑seq. Among these, the expression of ~87 lncRNAs was upregulated and 21 lncRNAs was downregulated in mature dendritic cell‑derived exosomes (Dex) compared with immature Dex. GO analyses indicated the involvement of upregulated lncRNAs in multiple biological functions, such as the immune system process, while downregulated lncRNAs were involved in poly(A) RNA binding. Analysis of the KEGG pathway identified the relationship of TNF signaling and ribosome pathway with upregulated lncRNAs and downregulated lncRNAs, respectively. The results of gene set enrichment analysis identified that three lncRNA‑associated transcripts (Procr‑203, Clec4e‑202 and Traf1‑203) were highly associated with immunoregulatory functions including T helper cell differentiation and Janus kinase‑STAT signaling pathway. The results indicated the involvement of candidate lncRNAs in immunoregulation and suggested a new perspective on the modulation of lncRNAs in Dex.

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