Department of Pulmonary and Critical Care Medicine, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
J Cell Mol Med. 2021 Aug;25(16):8062-8073. doi: 10.1111/jcmm.16737. Epub 2021 Jun 27.
Long non-coding ribonucleic acids (lncRNAs) play critical roles in acute lung injury (ALI). We aimed to explore the involvement of lncRNA HOX transcript antisense intergenic ribonucleic acid (HOTAIR) in regulating autophagy in lipopolysaccharide (LPS)-induced ALI. We obtained 1289 differentially expressed lncRNAs or messenger RNAs (mRNAs) via microarray analysis. HOTAIR was significantly upregulated in the LPS stimulation experimental group. HOTAIR knockdown (si-HOTAIR) promoted cell proliferation in LPS-stimulated A549 and BEAS-2B cells, suppressing the protein expression of autophagy marker light chain 3B and Beclin-1. Inhibition of HOTAIR suppressed LPS-induced cell autophagy, apoptosis and arrested cells in the G0/G1 phase prior to S phase entry. Further, si-HOTAIR alleviated LPS-induced lung injury in vivo. We predicted the micro-ribonucleic acid miR-17-5p to target HOTAIR and confirmed this via RNA pull-down and dual luciferase reporter assays. miR-17-5p inhibitor treatment reversed the HOTAIR-mediated effects on autophagy, apoptosis, cell proliferation and cell cycle. Finally, we predicted autophagy-related genes (ATGs) ATG2, ATG7 and ATG16 as targets of miR-17-5p, which reversed their HOTAIR-mediated protein upregulation in LPS-stimulated A549 and BEAS-2B cells. Taken together, our results indicate that HOTAIR regulated apoptosis, the cell cycle, proliferation and autophagy through the miR-17-5p/ATG2/ATG7/ATG16 axis, thus driving LPS-induced ALI.
长链非编码核糖核酸（lncRNAs）在急性肺损伤（ALI）中发挥关键作用。我们旨在探讨 lncRNA HOX 转录物反义基因间核糖核酸（HOTAIR）在调节脂多糖（LPS）诱导的 ALI 中的自噬作用。我们通过微阵列分析获得了 1289 个差异表达的 lncRNA 或信使 RNA（mRNA）。HOTAIR 在 LPS 刺激实验组中显著上调。HOTAIR 敲低（si-HOTAIR）促进 LPS 刺激的 A549 和 BEAS-2B 细胞增殖，抑制自噬标志物轻链 3B 和 Beclin-1 的蛋白表达。抑制 HOTAIR 抑制 LPS 诱导的细胞自噬、凋亡，并在 S 期进入之前将细胞阻滞在 G0/G1 期。此外，si-HOTAIR 在体内减轻 LPS 诱导的肺损伤。我们预测 micro-RNA miR-17-5p 靶向 HOTAIR，并通过 RNA 下拉和双荧光素酶报告基因实验证实了这一点。miR-17-5p 抑制剂处理逆转了 HOTAIR 对自噬、凋亡、细胞增殖和细胞周期的调节作用。最后，我们预测自噬相关基因（ATGs）ATG2、ATG7 和 ATG16 是 miR-17-5p 的靶基因，逆转了它们在 LPS 刺激的 A549 和 BEAS-2B 细胞中 HOTAIR 介导的蛋白上调。综上所述，我们的研究结果表明，HOTAIR 通过 miR-17-5p/ATG2/ATG7/ATG16 轴调节凋亡、细胞周期、增殖和自噬，从而驱动 LPS 诱导的 ALI。
