环状 RNA 表达谱分析及 hsa_circ_0007608 和 hsa_circ_0064656 作为 COPD-PH 患者潜在生物标志物的鉴定。
Expression Profiles of circRNAs and Identification of hsa_circ_0007608 and hsa_circ_0064656 as Potential Biomarkers for COPD-PH Patients.
机构信息
The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, 214023, People's Republic of China.
Transplant Centre, the Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, 214023, People's Republic of China.
出版信息
Int J Chron Obstruct Pulmon Dis. 2023 Nov 7;18:2457-2471. doi: 10.2147/COPD.S424712. eCollection 2023.
INTRODUCTION
Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD), which can worsen the prognosis and increase the mortality of COPD patients. Circular RNA (circRNA) has been discovered to participate in the occurrence and progression of PH in COPD and may have significant prospects for advanced diagnostics and prognosis evaluation. However, the expression profile of circRNAs in human lung tissues with definite diagnosis of COPD-PH remains to be further explored and validated.
METHODS
Twelve human lung tissue samples (6 each from COPD-PH and control groups) were collected and subjected to high-throughput sequencing. QRT-PCR was performed to validate the differential expression levels of the top 10 dysregulated circRNAs in patients' plasma samples, HPAECs and HPASMCs. Functional and pathway enrichment analysis on target genes was performed to explore the potential functions and pathways of those circRNAs. Hub genes obtained after conducting bioinformatics analysis on the predicted target mRNAs were verified by qRT-PCR in HPAECs and HPASMCs, and then we selected VCAN as a potential key gene involved in the pathogenesis of COPD-PH for immunohistochemistry validation in lung tissue.
RESULTS
A total of 136 circRNAs (39 up-regulated and 97 down-regulated) were differentially expressed between the two groups. Following qRT-PCR validation, two circRNAs (hsa_circ_0007608 and hsa_circ_0064656) were believed to be involved in the pathogenesis. GO and KEGG pathway analysis suggested that these two DECs were mainly related to the celluar proliferation, migration and EndMT. PPI network revealed 11 pairs of key mRNAs. VCAM1, VCAN and THBS1, three hub mRNAs with the highest reliability among all, were validated and proven to be up-regulated in COPD-PH. We innovatively found that VCAN may be involved in COPD-PH.
CONCLUSION
This study identified the functional circRNAs, providing insights into the molecular mechanisms and predictions of COPD-PH, and may provide potential diagnostic biomarkers or therapeutic targets for COPD-PH.
简介
肺动脉高压（PH）是慢性阻塞性肺疾病（COPD）的常见并发症，可使 COPD 患者的预后恶化并增加死亡率。环状 RNA（circRNA）已被发现参与 COPD 中 PH 的发生和发展，并且在高级诊断和预后评估方面可能具有重要前景。然而，具有明确 COPD-PH 诊断的人肺组织中 circRNA 的表达谱仍有待进一步探索和验证。
方法
收集 12 个人肺组织样本（每组 6 例，分别来自 COPD-PH 和对照组）进行高通量测序。在患者的血浆样本、HPAECs 和 HPASMCs 中进行 QRT-PCR 以验证前 10 个差异表达 circRNA 的差异表达水平。对靶基因进行功能和途径富集分析，以探索这些 circRNA 的潜在功能和途径。对预测靶 mRNA 进行生物信息学分析后，在 HPAECs 和 HPASMCs 中验证获得的 hub 基因，然后选择 VCAN 作为参与 COPD-PH 发病机制的潜在关键基因进行肺组织免疫组化验证。
结果
两组之间共有 136 个 circRNA（39 个上调和 97 个下调）差异表达。经 qRT-PCR 验证，认为两个 circRNA（hsa_circ_0007608 和 hsa_circ_0064656）与发病机制有关。GO 和 KEGG 途径分析表明，这两个 DEC 主要与细胞增殖、迁移和 EndMT 有关。PPI 网络揭示了 11 对关键 mRNAs。在所有 mRNAs 中，VCAM1、VCAN 和 THBS1 这三个可靠性最高的 hub mRNAs 得到验证并证明在 COPD-PH 中上调。我们创新性地发现 VCAN 可能参与了 COPD-PH。
结论
本研究鉴定了功能 circRNA，为 COPD-PH 的分子机制和预测提供了新的思路，并可能为 COPD-PH 提供潜在的诊断生物标志物或治疗靶点。
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