鉴定外周血单个核细胞中环状 RNA 相关 ceRNA 网络作为慢性阻塞性肺疾病潜在生物标志物。

Identification of circRNA-associated ceRNA networks in peripheral blood mononuclear cells as potential biomarkers for chronic obstructive pulmonary disease.

机构信息

College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong 518055, PR China.

Department of Preventive Medicine, Shantou University Medical College, Shantou, Guangdong 515041, PR China.

出版信息

Biosci Rep. 2023 Oct 31;43(10). doi: 10.1042/BSR20230005.

DOI:10.1042/BSR20230005

PMID:37650285

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10619198/

Abstract

Chronic obstructive pulmonary disease (COPD), which is a common respiratory disorder with high morbidity and mortality globally, has a complex pathogenesis that is not fully understood. Some circular RNAs (circRNAs) have been recognized to serve as miRNA sponges for regulating target RNA transcripts during the processes of human diseases. In the present study, we aimed to investigate novel circRNA-associated biomarkers for COPD, 245 differentially expressed circRNAs were identified, including 111 up-regulated and 134 down-regulated circRNAs. These candidate circRNAs were enriched in inflammation-associated pathways (such as mTOR, B-cell receptor, and NF-κB signaling pathways) via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. A combination of two circRNAs (up-regulated hsa_circ_0067209 and down-regulated hsa_circ_0000673) demonstrated good diagnostic value (area under the receiver operating characteristic curve [AUC] = 0.866) for COPD by receiver operating characteristic curve (ROC) analysis and qRT-PCR validation. Subsequently, hsa-miR-8082 and hsa-miR-1248 were identified as targets for hsa_circ_0067209 and hsa_circ_0000673, respectively, via bioinformatics analysis and a dual-luciferase reporter assay, and the combination of these two miRNAs displayed better diagnosis potential for COPD (AUC = 0.967) than each other. Evaluation of COPD-related mRNA profiles revealed that the up-regulated genes ABR and TRPM6 were predicted downstream targets for hsa_circ_0067209/hsa-miR-8082, whereas the down-regulated gene RORC was a predicted downstream target for hsa_circ_0000673/hsa-miR-1248. In summary, hsa_circ_0067209 and hsa_circ_0000673 have potential as novel diagnostic biomarkers of COPD. In addition, competing endogenous RNA networks of hsa_circ_0067209/hsa-miR-8082/ABR/TRPM6 and hsa_circ_0000673/hsa-miR-1248/RORC may play critical regulation roles for COPD pathogenesis.

摘要

慢性阻塞性肺疾病（COPD）是一种常见的呼吸道疾病，具有高发病率和死亡率，其发病机制复杂，尚未完全阐明。一些环状 RNA（circRNA）已被认为可作为 miRNA 海绵，在人类疾病的过程中调节靶 RNA 转录。本研究旨在探讨 COPD 的新型环状 RNA 相关生物标志物，鉴定出 245 个差异表达的 circRNA，包括 111 个上调和 134 个下调的 circRNA。通过基因本体论和京都基因与基因组百科全书富集分析，这些候选 circRNA 富集在炎症相关途径（如 mTOR、B 细胞受体和 NF-κB 信号通路）中。通过Receiver Operating Characteristic Curve（ROC）分析和 qRT-PCR 验证，两个 circRNA（上调的 hsa_circ_0067209 和下调的 hsa_circ_0000673）的组合显示出良好的 COPD 诊断价值（ROC 曲线下面积[AUC] = 0.866）。随后，通过生物信息学分析和双荧光素酶报告基因检测，确定 hsa-miR-8082 和 hsa-miR-1248 分别为 hsa_circ_0067209 和 hsa_circ_0000673 的靶基因，并且这两个 miRNA 的组合对 COPD 的诊断潜力优于各自（AUC = 0.967）。COPD 相关 mRNA 谱的评估表明，上调基因 ABR 和 TRPM6 被预测为 hsa_circ_0067209/hsa-miR-8082 的下游靶基因，而下调基因 RORC 则被预测为 hsa_circ_0000673/hsa-miR-1248 的下游靶基因。总之，hsa_circ_0067209 和 hsa_circ_0000673 可能成为 COPD 的新型诊断生物标志物。此外，hsa_circ_0067209/hsa-miR-8082/ABR/TRPM6 和 hsa_circ_0000673/hsa-miR-1248/RORC 的竞争性内源 RNA 网络可能在 COPD 发病机制中发挥关键调节作用。