OBJECTIVE This investigation was intended to elucidate lncRNA-miRNA networks that could explain inflammation underlying sepsis progression. METHODS In the first place, four kinds of mice models were established, namely, SHAM group (n = 30), trauma (TH) group (n = 30), lipopolysaccharide (LPS) group (n = 30) and TH + LPS group (n = 30). Their lung, spleen and liver tissues were gathered for determination of TNF-α, IL-6, IL-10 and MCP-1 levels. Furthermore, mouse mononuclear macrophage leukemia cell line (RAW264.7) was stimulated by LPS to establish inflammation cell models. Then si-NEAT1s, pcDNA3.1-NEAT1, miR-495-3p mimic, miR-495-3p inhibitor, miR-NC, miR-211 mimic and miR-211 inhibitor were, respectively, transfected into the cells, so as to observe the impacts of NEAT1, miR-495-3p and miR-211 on cytokine levels released by the cells. RESULTS The survival condition of mice in the TH + LPS group was undesirable, in relative to mice in the LPS group and SHAM group (both P < 0.05). High-level NEAT1 and low-level miR-495-3p/miR-211 were associated with poor survival of mice in the TH+LPS group (P < 0.05). Additionally, the correlation between NEAT1/miR-495-3p/miR-211 level and cytokine level was the strongest among TH+LPS-treated mice, in comparison to mice treated by TH or LPS. Furthermore, up-regulation of NEAT1 level and down-regulation of miR-495-3p/miR-211 level could aggravate inflammation in LPS-treated RAW264.7 cells. The miR-495-3p and miR-211 herein, were both subjected to sponging of NEAT1, possibly affected inflammation responses in RAW264.7 cells, respectively, through modulating STAT3 and PI3K/AKT signaling. CONCLUSION LncRNA NEAT1 exhibited great potential sepsis diagnosis and treatment, considering its modifying miR-495-3p/STAT3 axis and miR-211/PI3K/AKT axis in inflammation cell models.

中文翻译：

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LncRNA NEAT1逆转了miR-495-3p / STAT3轴和miR-211 / PI3K / AKT轴对败血症相关炎症的阻碍作用。

目的本研究旨在阐明lncRNA-miRNA网络，该网络可解释脓毒症进展的潜在炎症。方法首先建立SHAM组（n = 30），创伤（TH）组（n = 30），脂多糖（LPS）组（n = 30）和TH + LPS组四种小鼠模型。 （n = 30）。收集他们的肺，脾和肝组织以测定TNF-α，IL-6，IL-10和MCP-1的水平。此外，LPS刺激小鼠单核巨噬细胞白血病细胞系（RAW264.7）以建立炎症细胞模型。然后分别将si-NEAT1，pcDNA3.1-NEAT1，miR-495-3p模拟物，miR-495-3p抑制剂，miR-NC，miR-211模拟物和miR-211抑制剂转染到细胞中，从而观察NEAT1，miR-495-3p和miR-211对细胞释放的细胞因子水平的影响。结果与LPS组和SHAM组的小鼠相比，TH + LPS组的小鼠的生存状况不理想（均P <0.05）。高水平的NEAT1和低水平的miR-495-3p / miR-211与TH + LPS组小鼠的不良存活有关（P <0.05）。另外，与TH或LPS治疗的小鼠相比，在TH + LPS治疗的小鼠中，NEAT1 / miR-495-3p / miR-211水平与细胞因子水平之间的相关性最强。此外，NEAT1水平的上调和miR-495-3p / miR-211水平的下调可能加剧LPS处理的RAW264.7细胞的炎症。通过调节STAT3和PI3K / AKT信号，分别对miR-495-3p和miR-211进行NEAT1的海绵化处理，可能分别影响了RAW264.7细胞中的炎症反应。