Chen Weiwei, Zhu Ying, Niu Sihua, Zhou Yan, Chang Jian, Gan Shujie
Department of Nursing, Shanghai General Hospital, Shanghai Jiao Tong University School of Nursing, Shanghai, China.
Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Cardiovasc Med. 2025 Jun 30;12:1578711. doi: 10.3389/fcvm.2025.1578711. eCollection 2025.
Deep vein thrombosis (DVT) is the third most common cardiovascular disorder and can lead to high mortality and morbidity. This study aimed to clarify the molecular and immune characteristics of circular RNAs (circRNAs) and messenger RNAs (mRNAs) in DVT progression.
DVT-associated dataset GSE148333 was downloaded to screen differentially expressed circRNAs and mRNAs using the limma package. DVT-related modules/genes were then filtered using WGCNA. Subsequently, key hub genes associated with DVT were determined using four algorithms: MCC, MNC, EPC, and DEGREE. A circRNA-miRNA-hub gene network was then constructed, and the relationship between the DVT-related hub genes and immunity was analyzed. Finally, a DVT rat model was established to verify the expression of critical circRNAs and hub genes using real-time quantitative PCR.
A total of 421 circRNAs and 1,082 mRNAs were differentially expressed in DVT. Among these, 235 circRNAs and 207 mRNAs were identified as DVT-related and were significantly enriched in signaling pathways including NOD-like receptor, mTOR, FoxO, p53, and cell cycle. Thereafter, 17 important hub genes were obtained, including , , , , , , , , , , , , , , , , and . Subsequently, 227 circRNA-miRNA pairs and 84 miRNA-hub gene pairs were included to construct a circRNA-miRNA-hub gene network, containing CBT15_circR_28491-rno-miR-139-3p-//. Eight immune cell types showed differential infiltration levels in DVT and controls, with T helper cells positively related with all 17 hub genes.
This study offers valuable information about circRNAs and mRNAs in DVT, identifying CBT15_circR_28491-rno-miR-139-3p-// as a potential target for DVT management.
深静脉血栓形成（DVT）是第三常见的心血管疾病，可导致高死亡率和高发病率。本研究旨在阐明环状RNA（circRNA）和信使RNA（mRNA）在DVT进展中的分子和免疫特征。
下载DVT相关数据集GSE148333，使用limma软件包筛选差异表达的circRNA和mRNA。然后使用WGCNA筛选DVT相关模块/基因。随后，使用四种算法（MCC、MNC、EPC和DEGREE）确定与DVT相关的关键枢纽基因。接着构建circRNA-miRNA-枢纽基因网络，并分析DVT相关枢纽基因与免疫的关系。最后，建立DVT大鼠模型，使用实时定量PCR验证关键circRNA和枢纽基因的表达。
共有421个circRNA和1082个mRNA在DVT中差异表达。其中，235个circRNA和207个mRNA被鉴定为与DVT相关，并在包括NOD样受体、mTOR、FoxO、p53和细胞周期等信号通路中显著富集。此后，获得了17个重要的枢纽基因，包括 ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， 和 。随后，纳入227对circRNA-miRNA对和84对miRNA-枢纽基因对构建circRNA-miRNA-枢纽基因网络，包含CBT15_circR_28491-rno-miR-139-3p-//。八种免疫细胞类型在DVT和对照组中显示出不同的浸润水平，辅助性T细胞与所有17个枢纽基因呈正相关。
本研究提供了关于DVT中circRNA和mRNA的有价值信息，确定CBT15_circR_28491-rno-miR-139-3p-//为DVT治疗的潜在靶点。
