Shi Xue-Min, Bai Yu-Chao, Gao Yan-Rong, Bu Ning, Song Hai-Yan, Huang Li-Hua, Zhao Yu-Hang, Wang Su-Hua
School of Public Health, Baotou Medical College, Baotou, China.
Front Genet. 2021 Jul 19;12:700398. doi: 10.3389/fgene.2021.700398. eCollection 2021.
Rare-earth pneumoconiosis (REP) is the main occupational disease of rare earth exposed workers and there is no specific treatment. In this study, we performed high-throughput sequencing on the plasma of nine REP to describe and analyze the expression profiles of long non-coding RNA (lncRNA), micro RNA (miRNA) and mRNA and investigate their regulatory networks. Our results identified a total of 125 lncRNAs, 5 miRNAs, and 82 mRNAs were differentially expressed in the plasma of patients with REP. Furthermore, Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to analyze the differentially expressed non-coding RNAs (ncRNA). We found the differential expression of ncRNA are mainly related to the response of cells to stimulation, Hedgehog signaling pathway and so on. We also constructed lncRNA-miRNA-mRNA networks to further explore their underlying mechanism and possible relationships in REP. We found that in the competitive endogenous RNA (ceRNA) networks, lncRNA acts as a sponge of miRNA to regulate the target gene. The expression results were verified by qRT-PCR and the protein interaction networks of differentially expressed genes were constructed via the STRING database. OncoLnc online platform was used to do the lung cancer survival analysis among the top five mRNA analyzed by Protein-protein interaction (PPI) network analysis. We found miR-16-2-3p may used as biomarker for REP, because it is closely related to the occurrence and prognosis of REP through inflammatory reaction and in lung squamous cell carcinoma, its expression levels were positively correlated with the overall survival rate of patients.
稀土尘肺(REP)是稀土暴露工人的主要职业病,且尚无特效治疗方法。在本研究中,我们对9例REP患者的血浆进行了高通量测序,以描述和分析长链非编码RNA(lncRNA)、微小RNA(miRNA)和信使RNA(mRNA)的表达谱,并研究它们的调控网络。我们的结果表明,REP患者血浆中共有125种lncRNA、5种miRNA和82种mRNA差异表达。此外,利用本体论(GO)和京都基因与基因组百科全书(KEGG)分析对差异表达的非编码RNA(ncRNA)进行分析。我们发现ncRNA的差异表达主要与细胞对刺激的反应、刺猬信号通路等有关。我们还构建了lncRNA-miRNA-mRNA网络,以进一步探索它们在REP中的潜在机制和可能的关系。我们发现,在竞争性内源RNA(ceRNA)网络中,lncRNA作为miRNA的海绵来调控靶基因。通过qRT-PCR验证了表达结果,并通过STRING数据库构建了差异表达基因的蛋白质相互作用网络。利用OncoLnc在线平台对通过蛋白质-蛋白质相互作用(PPI)网络分析得到的前5种mRNA进行肺癌生存分析。我们发现miR-16-2-3p可能作为REP的生物标志物,因为它通过炎症反应与REP的发生和预后密切相关,并且在肺鳞状细胞癌中,其表达水平与患者的总生存率呈正相关。