Transcriptional profiling of exosomes derived from serum of patients with rare earth pneumoconiosis by RNA-sequencing and PI3K/Akt pathway is activated in lung of mice exposed to rare earth Nd2O3.

Abstract

Rare earth is used extensively around the world, and rare earth particles cause a respiratory disease in workers termed rare earth pneumoconiosis(REP) that have attracted considerable attention. However, the mechanisms of REP, characterized by diffuse pulmonary fibrosis, are elusive. REP progression involves various signaling pathway networks comprising numerous cell types and cytokines. Acting as an important medium for communication between cells, exosomes are emerging as a major research topic. However, the role of exosomal lncRNAs, miRNAs and mRNAs in REP remains unclear. In the present study, we conducted high-throughput RNA sequencing to generate long non-coding RNA(lncRNA), microRNA (miRNA) and mRNA profiles from the serum exosomes of nine patients with rare earth pneumoconiosis and nine healthy people. Our results identified a total of 94 lncRNAs, 93miRNAs, and 29 mRNAs were differentially expressed in the serum exosomes of patients with rare earth pneumoconiosis. Subsequently, Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to analyze the differentially expressed RNAs. The abundant enriched GO terms of exosomal genes are cytoplasm, protein binding, cytoskeleton, Nuclear cytoplasmic transport, and KEGG pathways of exosomal genes included metabolic and cancer pathway, PI3K/Akt, wnt, mTOR, HIF-1, actin cytoskeleton and cell cycle and so on. RT-qPCR results showed that lnc-KCNMB2-AS1, hsa-miR-186-5p, hsa-miR-100-5p, hsa-miR-381-5p, NCOA4 and PLXDC1 were up-regulated, and lnc-TMEM151A, hsa-miR-758-5p and hsa-miR-6842-5p were significantly down-regulated in exosomes. In addition, our study fuond that the PI3K/Akt pathway was activated, and the expression level of miR-100-5p was increased synchronously in lung tissue of mice exposed to rare earth Nd₂O₃. In this study, PI3K/Akt pathway is significant helpful in elucidating the mechanism of REP. These findings can provide new insights into the mechanism of REP and develop a novel treatment strategy and biomarker.