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hsa_circ_0006892 在急性呼吸窘迫综合征合并肺纤维化中的临床意义及潜在机制。

Clinical significance and potential mechanism of hsa_circ_0006892 in acute respiratory distress syndrome complicated with pulmonary fibrosis.

机构信息

Department of Dermatology, Postdoctoral Station of Clinical Medicine, The Third Xiangya Hospital of Central South University, Changsha, Hunan, 410013, China.

Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, Hubei Province, 430071, People's Republic of China.

出版信息

Mol Biol Rep. 2024 Nov 4;51(1):1120. doi: 10.1007/s11033-024-10047-0.

DOI:10.1007/s11033-024-10047-0
PMID:39495350
Abstract

BACKGROUND

Acute respiratory distress syndrome (ARDS) is a serious acute lung injury, and can develop into pulmonary fibrosis (PLF). Circular RNAs (circRNAs) regulatory network in ARDS is important. The study explored the role of hsa_circ_0006892 in the occurrence of ARDS and the development of PLF.

METHODS

Hsa_circ_0006892 levels were verified in serum samples of 203 ARDS patients with or without PLF, and the diagnostic value was evaluated through ROC. Cox regression analysis was performed to identify PLF-related factors. The downstream target genes were predicted online. The function and pathway of key genes were annotated through GO and KEGG pathway analysis. Protein-protein interaction (PPI) analysis was performed for the examination of protein interactions.

RESULTS

qRT-PCR determined the downregulation of hsa_circ_0006892 in the serum of both ARDS and PLF patients. Hsa_circ_0006892 can differentiate ARDS from controls, and independently related to the development of PLF. Nine targeted related miRNAs were integrated with dysregulated miRNAs from GSE27430 dataset. Clinically, miR-486-3p was the only miRNA that was significantly different in both ARDS and PLF groups, and was determined to be the target of hsa_circ_0006892. 180 target genes of miR-486-3p were predicted, which were integrated with ARDS and PLF-related GSE84439 and GSE38958 datasets. Go and KEGG pathway analysis identified Ras signaling pathway as the most commonly enriched pathway in the overlapped genes.

CONCLUSIONS

The present results identified the differentially expressed hsa_circ_0006892 in ARDS and PLF, and suggested a possible molecular mechanism of hsa_circ_0006892/miR-486-3p axis.

摘要

背景

急性呼吸窘迫综合征(ARDS)是一种严重的急性肺损伤,可发展为肺纤维化(PLF)。环状 RNA(circRNA)在 ARDS 中的调控网络很重要。本研究探讨了 hsa_circ_0006892 在 ARDS 发生和 PLF 发展中的作用。

方法

在 203 例 ARDS 患者(有或无 PLF)的血清样本中验证 hsa_circ_0006892 水平,并通过 ROC 评估其诊断价值。采用 Cox 回归分析鉴定 PLF 相关因素。在线预测下游靶基因。通过 GO 和 KEGG 通路分析注释关键基因的功能和通路。进行蛋白质-蛋白质相互作用(PPI)分析以检查蛋白质相互作用。

结果

qRT-PCR 确定 hsa_circ_0006892 在 ARDS 和 PLF 患者血清中下调。hsa_circ_0006892 可区分 ARDS 与对照组,并与 PLF 的发生独立相关。整合来自 GSE27430 数据集的失调 miRNA,得到 9 个靶向相关 miRNA。临床研究中,miR-486-3p 是唯一在 ARDS 和 PLF 两组均显著不同的 miRNA,且被确定为 hsa_circ_0006892 的靶基因。预测 miR-486-3p 的 180 个靶基因,与 ARDS 和 PLF 相关的 GSE84439 和 GSE38958 数据集整合。GO 和 KEGG 通路分析确定 Ras 信号通路为重叠基因中最常富集的通路。

结论

本研究鉴定了 ARDS 和 PLF 中差异表达的 hsa_circ_0006892,并提出了 hsa_circ_0006892/miR-486-3p 轴的可能分子机制。

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