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解析 1 型糖尿病模型人胰岛组织外泌体中的 lncRNA-mRNA 竞争性调控网络揭示了外泌体 miRNA 标志物。

Dissecting lncRNA-mRNA competitive regulatory network in human islet tissue exosomes of a type 1 diabetes model reveals exosome miRNA markers.

机构信息

Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

Harbin Center for Disease Control and Prevention, Harbin Municipal Health Commission, Harbin, China.

出版信息

Front Endocrinol (Lausanne). 2022 Nov 9;13:1015800. doi: 10.3389/fendo.2022.1015800. eCollection 2022.

Abstract

BACKGROUND

Emerging evidence shows that exosomes play a crucial role in the occurrence and development of diabetes and its complications. The molecules in exosomes can be regarded as important markers for the diagnosis of diseases. However, it is presently unclear the pathological association mechanism between exosomes and diabetes.

RESULTS

In this study, transcriptome data and lncRNA regulatory association data of human pancreatic islet-derived exosome were integrated to construct the ceRNA network. Network analysis revealed that lncRNA with differential expression were primarily involved in islet insulin secretion signaling pathways, including Hippo, TGF-beta, Wnt, FOXO, Neurotrophin and ErbB signaling pathway. Further, combined with miRNA mediated competitive regulation and differential expression analysis results, potential markers of diabetes were revealed and validated in independent datasets. Finally, we analyzed the mechanisms of diabetes based on the competitive regulatory association and function of lncRNA.

CONCLUSION

Our results suggest that lncRNA such as lncRNA PVT1, LINC00960 and hsa-miR-107 might be involved in inflammation response in T1DM, and the former lncRNA chose in the present study may serve as novel biomarkers and potential targets for the diagnosis and treatment of T1DM.

摘要

背景

新出现的证据表明,外泌体在糖尿病及其并发症的发生和发展中起着关键作用。外泌体中的分子可以被视为疾病诊断的重要标志物。然而,目前尚不清楚外泌体与糖尿病之间的病理关联机制。

结果

在这项研究中,整合了人类胰岛衍生外泌体的转录组数据和 lncRNA 调控关联数据,构建了 ceRNA 网络。网络分析表明,具有差异表达的 lncRNA 主要参与胰岛胰岛素分泌信号通路,包括 Hippo、TGF-β、Wnt、FOXO、神经生长因子和 ErbB 信号通路。此外,结合 miRNA 介导的竞争性调节和差异表达分析结果,在独立数据集上验证和验证了糖尿病的潜在标志物。最后,我们基于 lncRNA 的竞争性调控关联和功能分析了糖尿病的发病机制。

结论

我们的研究结果表明,lncRNA 如 lncRNA PVT1、LINC00960 和 hsa-miR-107 可能参与了 T1DM 中的炎症反应,本研究中选择的前 lncRNA 可能作为 T1DM 诊断和治疗的新型生物标志物和潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32a4/9682028/7b8ef184cc7e/fendo-13-1015800-g001.jpg

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