Background: Pulmonary inflammatory response (PIR) is one of the prognostic risk factors of lung adenocarcinoma (LUAD), with a high mortality rate. Objective: This study aims to investigate prognostic microRNA (miRNA) to improve clinical prognosis prediction and postoperative inflammation treatment in LUAD patients. Method: About 201 differentially expressed microRNAs (DE-miRNAs) in LUAD were mined by differential analysis. Univariate/multivariate Cox analyses established and validated prognostic risk miRNAs in TCGA-LUAD. KEGG and GO were used to link risk signatures and biological functions. After 48 hours of exposure to 50 ng/mL LPS, the miR-584-5p/RAB23 regulatory network was verified in qRT-PCR, Western Blotting, and the Luciferase Reporter Assay in A549 cells. Results: MiR-584-5p and miR-101-3p were validated as riskscore correlated with LUAD patients’ 1-year survival (p < 0.001) and participate in multiple inflammation-related pathways. RAB23, a RAS oncogene, is involved in inflammatory MAPK signaling. Evidence suggests that miR-584-5p regulates inflammation in LUAD by targeting RAB23. A549 cells were transfected with the mimic and inhibitor of miR-584-5p, confirming the negative regulatory relationship between miR-584-5p and RAB23. In the A549 induced by LPS, either over-expression of miR-584-5p or knock-down of RAB23 expression decreased the expression of inflammatory factors and increased cell viability. Conclusion: Prognostic-related risk miR-584-5p can regulate the expression of RAB23 at both the mRNA and protein levels, thereby influencing the development of a PIR in LUAD. This will have significant implications for the clinical prognosis prediction and therapy decision-making of LUAD patients with PIR.

中文翻译：

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LUAD 中肺部炎症反应的生物标志物：miR-584-5p 靶向 RAB23 抑制 A549 细胞中 LPS 诱导的炎症

背景：肺部炎症反应（PIR）是肺腺癌（LUAD）的预后危险因素之一，具有较高的死亡率。目的：本研究旨在研究预后 microRNA (miRNA)，以改善 LUAD 患者的临床预后预测和术后炎症治疗。方法：通过差异分析挖掘LUAD中约201个差异表达的microRNA（DE-miRNA）。单变量/多变量 Cox 分析在 TCGA-LUAD 中建立并验证了预后风险 miRNA。KEGG 和 GO 用于将风险特征和生物功能联系起来。暴露于 50 ng/mL LPS 48 小时后，通过 qRT-PCR、蛋白质印迹和荧光素酶报告基因检测在 A549 细胞中验证了 miR-584-5p/RAB23 调控网络。结果：miR-584-5p 和 miR-101-3p 被验证为与 LUAD 患者 1 年生存率相关的风险评分 (p < 0.001)，并参与多种炎症相关途径。RAB23 是一种 RAS 癌基因，参与炎症 MAPK 信号传导。有证据表明 miR-584-5p 通过靶向 RAB23 来调节 LUAD 中的炎症。用miR-584-5p的模拟物和抑制剂转染A549细胞，证实了miR-584-5p和RAB23之间的负调控关系。在 LPS 诱导的 A549 中，miR-584-5p 的过表达或 RAB23 表达的敲低都会降低炎症因子的表达并增加细胞活力。结论：预后相关风险 miR-584-5p 可以在 mRNA 和蛋白水平上调节 RAB23 的表达，从而影响 LUAD 中 PIR 的发生。这将对伴有 PIR 的 LUAD 患者的临床预后预测和治疗决策产生重大影响。