Comprehensive Analysis of LncRNA-mRNA Expression Profiles and the ceRNA Network Associated with Pyroptosis in LPS-Induced Acute Lung Injury.
Comprehensive Analysis of LncRNA-mRNA Expression Profiles and the ceRNA Network Associated with Pyroptosis in LPS-Induced Acute Lung Injury.
复制标题
DOI：
10.2147/jir.s297081
复制
发表时间：
2021
影响因子：
4.5
通讯作者：
Qian K
中科院分区：
文献类型：
--
作者：
Luo D;Liu F;Zhang J;Shao Q;Tao W;Xiao R;Dai W;Ding C;Qian K
目的探讨脂多糖（LPS）诱导的急性肺损伤（ALI）的分子机制，并在基因表达谱中寻找与细胞凋亡相关的lncRNA和mRNA。我们研究了脂多糖（LPS）诱导的ALI早期lncRNA和mRNA的表达。进行RNA测序（RNA-Seq）以分析LPS诱导组和对照组之间的lncRNA和mRNA表达谱。我们利用生物信息学分析方法对获得的差异mRNA中的早期差异lncRNA的靶基因进行预测。在早期ALI模型中，总共有78个lncRNA和248个mRNA在2小时上调，9小时下调，21个lncRNA和107个mRNA在2小时下调，9小时上调。我们预测了前20个lncRNA中的7个顺式和反式调控靶基因。基因本体论（GO）分析表明，筛选的lncRNA的靶基因在三个方面最丰富：蛋白丝氨酸/苏氨酸激酶活性的调节、百日咳和细胞对LPS的反应。另外，通过京都基因和基因组百科全书（KEGG）分析，lncRNA的靶基因是在百日咳、破骨细胞分化和cAMP信号通路中富集的前三个。我们还鉴定了重要的mRNA和lncRNA。蛋白质-蛋白质相互作用（PPI）网络分析表明，Tnf、Jun和Atf 3是影响该基因表达的前三位关键基因。在体外验证了Hub lncRNA 4344（NONRATT004344.2）和顺式调节靶mRNA（NLRP 3）。最后，荧光素酶测定结果证实，lncRNA 4344通过靶向NLRP 3吸收miR-138- 5 p以促进对LPS诱导的急性肺损伤的炎症反应中的焦亡。基于通过RNA-Seq分析lncRNA和mRNA表达谱以及实验验证，本研究首次揭示lncRNA 4344通过靶向NLRP 3吸收miR-138- 5 p以促进LPS诱导的急性肺损伤的炎症反应中的焦亡。这些新发现的lncRNA、miRNA和mRNA可能成为早期治疗和预防ALI的新靶点。
To explore the molecular mechanism and search for candidate lncRNA and mRNA associated with pyroptosis in the gene expression profile of LPS-induced acute lung injury (ALI). We investigated lncRNA and mRNA expression in lipopolysaccharide (LPS)-induced ALI at an early stage. RNA sequencing (RNA-Seq) was carried out to analyze lncRNA and mRNA expression profiles between the LPS-induced and control groups. We used bioinformatics analysis to predict target genes of early differential lncRNAs among obtained the differential mRNAs. A total of 78 lncRNAs and 248 mRNAs were upregulated at 2 hours and downregulated at 9 hours, and 21 lncRNAs and 107 mRNAs were downregulated at 2 and upregulated at 9 hours in early ALI models. We predicted 7 cis-and trans-regulated target genes of the top 20 lncRNAs. Gene Ontology (GO) analysis indicated that the target genes for the screened lncRNAs were most enriched in three-terms: regulation of protein serine/threonine kinase activity, pertussis, and cellular response to LPS. Additionally, target genes of lncRNAs were the top three enriched in pertussis, osteoclast differentiation, and cAMP signaling pathways with Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. We also identified vital mRNAs and lncRNAs. Protein-protein interaction (PPI) network analysis suggested that Tnf, Jun, and Atf3 were the top three key genes. Hub lncRNA4344 (NONRATT004344.2) and cis-regulated target mRNA (NLRP3) were validated in vitro. Finally, luciferase assay results confirmed that lncRNA4344 sponged miR‐138-5p to promote pyroptosis in inflammatory responses to LPS‐induced acute lung injury by targeting NLRP3. Based on analysis of lncRNA and mRNA expression profiles by RNA-Seq and experimental verification, this study is the first to reveal that lncRNA4344 sponged miR‐138-5p to promote pyroptosis in inflammatory responses of LPS‐induced acute lung injury by targeting NLRP3. These newly identified lncRNA, miRNA, and mRNA might be novel potential targets for early treatment and prevention in early ALI.