Wu Xiaoling, Ma Chenjie, Ma Qinmei, Zhuang Peipei, Deng Guangcun
Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Ningxia University, Yinchuan 750021, China.
School of Life Science, Ningxia University, Yinchuan 750021, China.
Pathogens. 2022 May 2;11(5):532. doi: 10.3390/pathogens11050532.
Long noncoding RNAs (LncRNAs) play critical roles in many respiratory diseases. Acute respiratory distress syndrome (ARDS) is a destructive clinical syndrome of respiratory diseases. However, the potential mechanism of LncRNAs on ARDS remains largely unknown.
To identify the profiles of LncRNAs and mRNAs in the LPS-induced ARDS mouse model, the microarray analyses were hired to detect the expression of LncRNAs and mRNAs in present study. Subsequently, microarray data were verified by quantitative qRT-PCR. Functional annotation on DE mRNAs and LncRNAs were carried out by bioinformatics analysis. Furthermore, the role of selected DE LncRNAs on correlated genes was confirmed by si-RNA and Western blot.
The expression of 2110 LncRNAs and 2690 mRNAs were significantly changed, which were further confirmed by qRT-PCR. GO and KEGG analysis indicated that the up-regulated mRNAs were mainly related to a defense response and tumor necrosis factor (TNF) signaling pathway, respectively. LncRNA-mRNA co-expression analyses showed that LncRNAs NR_003508, ENSMUST00000131638, ENSMUST00000119467, and ENSMUST00000124853 may correlate to MLKL, RIPK3, RIPK1, Caspase1, and NLRP3, respectively, or cooperatively, which were highly involved in the cell necroptosis process. Furthermore, siRNA for NR_003508 confirmed the co-expression analyses results.
To summarize, this study implied that the DE LncRNAs could be potent regulators and target genes of ARDS and will provide a novel insight into the regulation of the pathogenesis of ARDS.
长链非编码RNA（LncRNAs）在多种呼吸系统疾病中发挥关键作用。急性呼吸窘迫综合征（ARDS）是一种具有破坏性的呼吸系统临床综合征。然而，LncRNAs在ARDS中的潜在机制仍 largely未知。
为了鉴定脂多糖诱导的ARDS小鼠模型中LncRNAs和mRNAs的表达谱，本研究采用微阵列分析来检测LncRNAs和mRNAs的表达。随后，通过定量qRT-PCR对微阵列数据进行验证。通过生物信息学分析对差异表达的mRNAs和LncRNAs进行功能注释。此外，通过小干扰RNA（si-RNA）和蛋白质免疫印迹法（Western blot）证实了所选差异表达LncRNAs对相关基因的作用。
2110个LncRNAs和2690个mRNAs的表达发生了显著变化，qRT-PCR进一步证实了这一点。基因本体（GO）和京都基因与基因组百科全书（KEGG）分析表明，上调的mRNAs分别主要与防御反应和肿瘤坏死因子（TNF）信号通路相关。LncRNA-mRNA共表达分析表明，LncRNAs NR_003508、ENSMUST00000131638、ENSMUST00000119467和ENSMUST00000124853可能分别或协同与混合谱系激酶结构域样蛋白（MLKL）、受体相互作用蛋白激酶3（RIPK3）、受体相互作用蛋白激酶1（RIPK1）、半胱天冬酶1（Caspase1）和NLR家族含pyrin结构域蛋白3（NLRP3）相关，这些蛋白高度参与细胞坏死性凋亡过程。此外，针对NR_003508的小干扰RNA证实了共表达分析结果。
总之，本研究表明差异表达的LncRNAs可能是ARDS的有效调节因子和靶基因，并将为ARDS发病机制的调控提供新的见解。
