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lncRNA-SNHG14 Plays a Role in Acute Lung Injury Induced by Lipopolysaccharide through Regulating Autophagy via miR-223-3p/Foxo3a
Mediators of Inflammation ( IF 4.6 ) Pub Date : 2021-09-08 , DOI: 10.1155/2021/7890288
Jun Hong 1, 2 , Shijing Mo 1, 2 , Fangxiao Gong 1, 2 , Zongbin Lin 1, 2 , Hanhui Cai 1, 2 , Ziqiang Shao 1, 2 , Xianghong Yang 1, 2 , Renhua Sun 1, 2 , Qiangnu Zhang 3 , Jingquan Liu 1, 2
Affiliation  

lncRNAs play important roles in lipopolysaccharide- (LPS-) induced acute lung injury. But the mechanism still needs further research. In the present study, we investigate the functional role of the lncRNA-SNHG14/miR-223-3p/Foxo3a pathway in LPS-induced ALI and tried to confirm its regulatory effect on autophagy. Transcriptomic profile changes were identified by RNA-seq in LPS-treated alveolar type II epithelial cells. The expression changes of lncRNA-SNHG14/miR-223-3p/Foxo3a were confirmed using qRT-PCR and west blot. The binding relationship of lncRNA-SNHG14/miR-223-3p/and miR-223-3p/Foxo3a was verified using dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays. Using gain-of-function or loss-of-function approaches, the effect of lncRNA-SNHG14/miR-223-3p/Foxo3a was investigated in LPS-induced acute lung injury mice model and in vitro. Increasing of lncRNA-SNHG14 and Foxo3a with reducing miR-223-3p was found in LPS-treated A549 cells and lung tissue collected from the LPS-induced ALI model. lncRNA-SNHG14 inhibited miR-223-3p but promoted Foxo3a expression as a ceRNA. Artificially changes of lncRNA-SNHG14/miR-223-3p/Foxo3a pathway promoted or protected cell injury from LPS in vivo and in vitro. Autophagy activity could be influenced by lncRNA-SNHG14/miR-223-3p/Foxo3a pathway in cells with or without LPS treatment. In conclusion, aberrant expression changes of lncRNA-SNHG14 participated alveolar type II epithelial cell injury and acute lung injury induced by LPS through regulating autophagy. One underlying mechanism is that lncRNA-SNHG14 regulated autophagy by controlling miR-223-3p/Foxo3a as a ceRNA. It suggested that lncRNA-SNHG14 may serve as a potential therapeutic target for patients with sepsis-induced ALI.

中文翻译:

lncRNA-SNHG14通过miR-223-3p/Foxo3a调控自噬在脂多糖诱导的急性肺损伤中发挥作用

lncRNA在脂多糖(LPS-)诱导的急性肺损伤中起重要作用。但其机制仍需进一步研究。在本研究中,我们研究了 lncRNA-SNHG14/miR-223-3p/Foxo3a 通路在 LPS 诱导的 ALI 中的功能作用,并试图证实其对自噬的调节作用。在 LPS 处理的肺泡 II 型上皮细胞中,通过 RNA-seq 鉴定了转录组谱的变化。lncRNA-SNHG14/miR-223-3p/Foxo3a的表达变化通过qRT-PCR和western印迹得到证实。lncRNA-SNHG14/miR-223-3p/和 miR-223-3p/Foxo3a 的结合关系通过双荧光素酶报告基因、RNA 免疫沉淀和 RNA 下拉分析进行验证。使用功能增益或功能损失方法,体外。在 LPS 处理的 A549 细胞和从 LPS 诱导的 ALI 模型收集的肺组织中发现 lncRNA-SNHG14 和 Foxo3a 增加而 miR-223-3p 减少。lncRNA-SNHG14 抑制 miR-223-3p,但促进 Foxo3a 作为 ceRNA 的表达。lncRNA-SNHG14/miR-223-3p/Foxo3a通路的人为改变在体内体外促进或保护细胞免受LPS损伤. 在有或没有 LPS 处理的细胞中,自噬活性可能受到 lncRNA-SNHG14/miR-223-3p/Foxo3a 通路的影响。综上所述,lncRNA-SNHG14的异常表达变化通过调节自噬参与了LPS诱导的肺泡II型上皮细胞损伤和急性肺损伤。一种潜在机制是 lncRNA-SNHG14 通过控制 miR-223-3p/Foxo3a 作为 ceRNA 来调节自噬。这表明 lncRNA-SNHG14 可作为脓毒症诱导的 ALI 患者的潜在治疗靶点。
更新日期:2021-09-08
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