Identification of a Plasma Exosomal lncRNA- and circRNA-Based ceRNA Regulatory Network in Patients With Lung Adenocarcinoma

IF 1.9 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal Pub Date : 2024-10-20 DOI:10.1111/crj.70026

Wangyu Zhu, Huafeng Zhang, Liwei Tang, Kexin Fang, Nawa Lin, Yanyan Huang, Yongkui Zhang, Hanbo Le

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引用次数: 0

Abstract

Background

Exosomes have been established to be enriched with various long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) that exert various biological effects. However, the lncRNA- and circRNA-mediated coexpression competing endogenous RNA (ceRNA) regulatory network in exosomes derived from the plasma of patients with lung adenocarcinoma (LUAD) remains elusive.

Methods and Results

This study enrolled nine patients with lung adenocarcinoma and three healthy individuals, and the differential expression of messenger RNAs (mRNAs), lncRNAs, and circRNAs was detected using microarray analysis, while microRNAs (miRNAs) were detected through RNA sequencing. Additionally, bioinformatics algorithms were applied to evaluate the lncRNA–miRNA–mRNAs/circRNA–miRNA–mRNA network. Differentially expressed cicRNAs were identified via quantitative reverse transcription polymerase chain reaction (RT-qPCR). A total of 1016 lncRNAs, 1396 circRNAs, 45 miRNAs, and 699 mRNAs were differentially expressed in the plasma exosomes of patients with LUAD compared with healthy controls. Among them, 881 lncRNAs were upregulated and 135 were downregulated, 916 circRNAs were upregulated while 480 were downregulated, 45 miRNAs were upregulated while none were downregulated, and 591 mRNAs were upregulated while 108 were downregulated (p ≤ 0.05, and fold change ≥ 2). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the biological functions of differentially expressed RNAs. Meanwhile, the RNA networks displayed the regulatory relationship between dysregulated RNAs. Finally, RT-qPCR validated that the expression of circ-0033861, circ-0043273, and circ-0011959 was upregulated in the plasma exosome of patients with LUAD compared to healthy controls (p = 0.0327, p = 0.0002, p = 0.0437, respectively).

Conclusion

This study proposed a newly discovered ncRNA–miRNA–mRNA/circRNA–miRNA–mRNA ceRNA network and identified that the expression of circulating circ-0033861, circ-0043273, and circ-0011959 was up-regulated in the plasma exosomes of patients with LUAD, offering valuable insights for exploring the potential function of exosomal noncoding RNA and identifying potential biomarkers for LUAD.

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鉴定肺腺癌患者血浆外泌体 lncRNA 和 circRNA 的 ceRNA 调控网络

背景：已证实外泌体富含各种长非编码RNA（lncRNA）和环状RNA（circRNA），可发挥各种生物学效应。然而，从肺腺癌（LUAD）患者血浆中提取的外泌体中，lncRNA和circRNA介导的共表达与内源性RNA（ceRNA）调控网络的竞争仍然难以捉摸：本研究招募了9名肺腺癌患者和3名健康人，利用芯片分析检测了信使RNA（mRNA）、lncRNA和circRNA的差异表达，并通过RNA测序检测了microRNA（miRNA）。此外，还应用生物信息学算法评估了 lncRNA-miRNA-mRNAs/circRNA-miRNA-mRNA 网络。通过定量反转录聚合酶链反应（RT-qPCR）鉴定了差异表达的cicRNA。与健康对照组相比，LUAD 患者血浆外泌体中共有 1016 个 lncRNA、1396 个 circRNA、45 个 miRNA 和 699 个 mRNA 存在差异表达。其中，881个lncRNA上调，135个下调；916个circRNA上调，480个下调；45个miRNA上调，无下调；591个mRNA上调，108个下调（P≤0.05，折合变化≥2）。基因本体（GO）分析和京都基因组百科全书（KEGG）通路分析揭示了差异表达的 RNA 的生物学功能。同时，RNA 网络显示了失调 RNA 之间的调控关系。最后，RT-qPCR验证了与健康对照组相比，circ-0033861、circ-0043273和circ-0011959在LUAD患者血浆外泌体中的表达上调（分别为p = 0.0327、p = 0.0002、p = 0.0437）：该研究提出了一个新发现的ncRNA-miRNA-mRNA/circRNA-miRNA-mRNA ceRNA网络，并确定了循环circ-0033861、circ-0043273和circ-0011959在LUAD患者血浆外泌体中的表达上调，为探索外泌体非编码RNA的潜在功能和确定LUAD的潜在生物标志物提供了有价值的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Respiratory Journal 医学-呼吸系统

CiteScore

3.70

自引率

0.00%

发文量

104

审稿时长

>12 weeks

期刊介绍： Overview Effective with the 2016 volume, this journal will be published in an online-only format. Aims and Scope The Clinical Respiratory Journal (CRJ) provides a forum for clinical research in all areas of respiratory medicine from clinical lung disease to basic research relevant to the clinic. We publish original research, review articles, case studies, editorials and book reviews in all areas of clinical lung disease including: Asthma Allergy COPD Non-invasive ventilation Sleep related breathing disorders Interstitial lung diseases Lung cancer Clinical genetics Rhinitis Airway and lung infection Epidemiology Pediatrics CRJ provides a fast-track service for selected Phase II and Phase III trial studies. Keywords Clinical Respiratory Journal, respiratory, pulmonary, medicine, clinical, lung disease, Abstracting and Indexing Information Academic Search (EBSCO Publishing) Academic Search Alumni Edition (EBSCO Publishing) Embase (Elsevier) Health & Medical Collection (ProQuest) Health Research Premium Collection (ProQuest) HEED: Health Economic Evaluations Database (Wiley-Blackwell) Hospital Premium Collection (ProQuest) Journal Citation Reports/Science Edition (Clarivate Analytics) MEDLINE/PubMed (NLM) ProQuest Central (ProQuest) Science Citation Index Expanded (Clarivate Analytics) SCOPUS (Elsevier)