Acute lung injury (ALI) is a fatal inflammatory response syndrome. LncRNA XIST (XIST) is a lung cancer-related gene and participates in pneumonia. However, whether XIST participates in lipopolysaccharides (LPS)-induced ALI remains unclear. LPS-induced inflammation model was constructed in vitro, then cell viability, cytokines, cell apoptosis, protein, and mRNA expressions were individually detected by cell counting kit-8, enzyme-linked immunosorbent assay and flow cytometry, Western blot, and qRT-PCR. A dual-luciferase reporter assay confirmed the relationships among XIST, miR-132-3p, and MAPK14. Furthermore, inflammation and conditions after knockdown of XIST were assessed by hematoxylin and eosin staining, lung wet-to-dry weight ratio, PaO₂/FiO₂ ratio, and malondialdehyde (MDA) contents using LPS-induced in vivo model. Our findings indicated that the LPS challenge decreased cell viability, increased cell apoptosis, and caused secretions of pro-inflammatory cytokines. Noticeably, LPS significantly upregulated XIST, MAPK14, and downregulated miR-132-3p. Mechanistically, XIST acted as a molecular sponge to suppress miR-132-3p, and MAPK14 was identified as a target of miR-132-3p. Functional analyses demonstrated that XIST silencing remarkably increased cell survival and alleviated cell death and lung injury through decreasing TNF-α, IL-1β, IL-6, accumulation of inflammatory cells, alveolar hemorrhage, MDA release, and increased PaO₂/FiO₂ ratio, as well as upregulating Bcl-2, and downregulating Bax, MAPK14, and p-extracellular signal-regulated kinases ½. In contrast, inhibition of the miR-132-3p antagonized the effects of XIST silencing. In conclusion, inhibition of XIST exhibited a protective role in LPS-induced ALI through modulating the miR-132-3p/MAPK14 axis.

急性肺损伤 (ALI) 是一种致命的炎症反应综合征。LncRNA XIST（XIST）是肺癌相关基因，参与肺炎。然而，XIST 是否参与脂多糖 (LPS) 诱导的 ALI 仍不清楚。体外构建LPS诱导的炎症模型，通过细胞计数kit-8、酶联免疫吸附法和流式细胞术、Western blot、qRT-PCR分别检测细胞活力、细胞因子、细胞凋亡、蛋白和mRNA表达。 . 双荧光素酶报告基因检测证实了 XIST、miR-132-3p 和 MAPK14 之间的关系。_{此外，通过苏木精和伊红染色、肺湿干重比、PaO 2} / FiO ₂评估 XIST 敲低后的炎症和状况使用 LPS 诱导的体内模型的比率和丙二醛 (MDA) 含量。我们的研究结果表明，LPS 攻击降低了细胞活力，增加了细胞凋亡，并导致促炎细胞因子的分泌。值得注意的是，LPS 显着上调 XIST、MAPK14 和下调 miR-132-3p。从机制上讲，XIST 充当分子海绵来抑制 miR-132-3p，而 MAPK14 被确定为 miR-132-3p 的靶标。功能分析表明，XIST 沉默通过减少 TNF-α、IL-1β、IL-6、炎症细胞的积累、肺泡出血、MDA 释放和增加 PaO ₂ /FiO _{2显着增加细胞存活并减轻细胞死亡和肺损伤}比率，以及上调 Bcl-2，下调 Bax、MAPK14 和 p-细胞外信号调节激酶 ½。相反，抑制 miR-132-3p 会拮抗 XIST 沉默的作用。总之，抑制 XIST 通过调节 miR-132-3p/MAPK14 轴在 LPS 诱导的 ALI 中表现出保护作用。