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脂多糖诱导的急性肺损伤(ALI)中差异 RNA 谱及相关竞争性内源性 RNA 网络的全转录组分析。

Whole transcriptome analysis of the differential RNA profiles and associated competing endogenous RNA networks in LPS-induced acute lung injury (ALI).

机构信息

School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.

Department of Critical Care Medicine, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.

出版信息

PLoS One. 2021 May 7;16(5):e0251359. doi: 10.1371/journal.pone.0251359. eCollection 2021.

Abstract

Acute lung injury (ALI) is a serious inflammation disease usually arises alveolar epithelial membrane dysfunction and even causes death. Therefore, the aims of this study are to screen the differentially expressed lncRNAs, circRNAs, miRNAs, and mRNAs in ALI based on the high-throughput sequencing. The lipopolysaccharide (LPS)-induced ALI mouse model was established, the injury of ALI mouse model was evaluated through histological analysis with hemotoxylin and eosin (H & E) staining assay, dry/wet ratio, infiltrated-immune cells, ET-1 mRNA expression and released-proinflammation factors. Then, expression data of lncRNAs, circRNAs, miRNAs and mRNAs in ALI were acquired using whole-transcriptome sequencing. The differential expression of lncRNAs (DE lncRNAs), circRNAs (DE circRNAs), miRNAs (DE miRNAs) and mRNAs (DE mRNAs) were identified, and the lncRNA-miRNA-mRNA network and circRNA-miRNA-mRNA network were constructed, and the biological function of target genes were annotated based on bioinformatics analysis. In the present study, the LPS-induced ALI mouse model was successfully established. The biological analysis results showed that total 201 DE lncRNAs, 172 DE circRNAs, 62 DE miRNAs, and 3081 DE mRNAs were identified in ALI. The 182 lncRNA-miRNA-mRNA networks and 32 circRNA-miRNA-mRNA networks were constructed were constructed based on the correlation between lncRNAs/circRNAs, miRNAs, mRNAs. The biological function analysis indicated that TNF signaling pathway, chemokine signaling pathway and so on involved in ALI. In the present study, the differential expression coding and non-coding RNAs (ncRNAs) in ALI were identified, and their regulatory networks were constructed. There might provide the potential biomarkers and underlying mechanism for ALI diagnosis and treatment.

摘要

急性肺损伤(ALI)是一种严重的炎症性疾病,通常源于肺泡上皮膜功能障碍,甚至导致死亡。因此,本研究旨在基于高通量测序筛选 ALI 中差异表达的长非编码 RNA(lncRNA)、环状 RNA(circRNA)、微小 RNA(miRNA)和信使 RNA(mRNA)。通过苏木精和伊红(H&E)染色检测、干湿比、浸润免疫细胞、内皮素-1(ET-1)mRNA 表达和释放促炎因子评估脂多糖(LPS)诱导的 ALI 小鼠模型的损伤。然后,使用全转录组测序获得 ALI 中 lncRNA、circRNA、miRNA 和 mRNA 的表达数据。鉴定 lncRNA(DE lncRNA)、circRNA(DE circRNA)、miRNA(DE miRNA)和 mRNA(DE mRNA)的差异表达,并构建 lncRNA-miRNA-mRNA 网络和 circRNA-miRNA-mRNA 网络,基于生物信息学分析注释靶基因的生物学功能。在本研究中,成功建立了 LPS 诱导的 ALI 小鼠模型。生物分析结果表明,在 ALI 中鉴定出 201 个 DE lncRNA、172 个 DE circRNA、62 个 DE miRNA 和 3081 个 DE mRNA。基于 lncRNA/circRNA、miRNA、mRNA 之间的相关性构建了 182 个 lncRNA-miRNA-mRNA 网络和 32 个 circRNA-miRNA-mRNA 网络。生物功能分析表明,肿瘤坏死因子(TNF)信号通路、趋化因子信号通路等参与了 ALI。在本研究中,鉴定了 ALI 中差异表达的编码和非编码 RNA(ncRNA),并构建了它们的调控网络。这可能为 ALI 的诊断和治疗提供潜在的生物标志物和潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0499/8104378/eefb72a0c4f5/pone.0251359.g001.jpg

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