NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases (First Affiliated Hospital, School of Medicine, Shihezi University), Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China.
Department of Cardiology, Jinhua Municipal Central Hospital, Jinhua, Zhejiang, China.
Genet Res (Camb). 2023 May 17;2023:8194338. doi: 10.1155/2023/8194338. eCollection 2023.
Calcific aortic valve disease (CAVD) is the most common native valve disease. Valvular interstitial cell (VIC) osteogenic differentiation and valvular endothelial cell (VEC) dysfunction are key steps in CAVD progression. Circular RNA (circRNAs) is involved in regulating osteogenic differentiation with mesenchymal cells and is associated with multiple disease progression, but the function of circRNAs in CAVD remains unknown. Here, we aimed to investigate the effect and potential significance of circRNA-miRNA-mRNA networks in CAVD.
Two mRNA datasets, one miRNA dataset, and one circRNA dataset of CAVD downloaded from GEO were used to identify DE-circRNAs, DE-miRNAs, and DE-mRNAs. Based on the online website prediction function, the common mRNAs (FmRNAs) for constructing circRNA-miRNA-mRNA networks were identified. GO and KEGG enrichment analyses were performed on FmRNAs. In addition, hub genes were identified by PPI networks. Based on the expression of each data set, the circRNA-miRNA-hub gene network was constructed by Cytoscape (version 3.6.1).
32 DE-circRNAs, 206 DE-miRNAs, and 2170 DE-mRNAs were identified. Fifty-nine FmRNAs were obtained by intersection. The KEGG pathway analysis of FmRNAs was enriched in pathways in cancer, JAK-STAT signaling pathway, cell cycle, and MAPK signaling pathway. Meanwhile, transcription, nucleolus, and protein homodimerization activity were significantly enriched in GO analysis. Eight hub genes were identified based on the PPI network. Three possible regulatory networks in CAVD disease were obtained based on the biological functions of circRNAs including: hsa_circ_0026817-hsa-miR-211-5p-CACNA1C, hsa_circ_0007215-hsa-miR-1252-5p-MECP2, and hsa_circ_0007215-hsa-miR-1343-3p- RBL1.
The present bionformatics analysis suggests the functional effect for the circRNA-miRNA-mRNA network in CAVD pathogenesis and provides new targets for therapeutics.
钙化性主动脉瓣疾病（CAVD）是最常见的原生瓣膜疾病。瓣膜间质细胞（VIC）成骨分化和瓣膜内皮细胞（VEC）功能障碍是 CAVD 进展的关键步骤。环状 RNA（circRNA）参与调节间充质细胞的成骨分化，并与多种疾病的进展相关，但 circRNA 在 CAVD 中的作用尚不清楚。本研究旨在探讨 CAVD 中 circRNA-miRNA-mRNA 网络的作用及潜在意义。
从 GEO 下载了两个 CAVD 的 mRNA 数据集、一个 miRNA 数据集和一个 circRNA 数据集，用于鉴定 DE-circRNAs、DE-miRNAs 和 DE-mRNAs。基于在线网站预测功能，鉴定构建 circRNA-miRNA-mRNA 网络的共同 mRNA（FmRNAs）。对 FmRNAs 进行 GO 和 KEGG 富集分析。此外，通过 PPI 网络鉴定枢纽基因。基于每个数据集的表达，通过 Cytoscape（版本 3.6.1）构建 circRNA-miRNA-枢纽基因网络。
鉴定出 32 个 DE-circRNAs、206 个 DE-miRNAs 和 2170 个 DE-mRNAs。通过交集获得 59 个 FmRNAs。FmRNAs 的 KEGG 通路分析富集在癌症、JAK-STAT 信号通路、细胞周期和 MAPK 信号通路。同时，GO 分析中显著富集转录、核仁、蛋白质同源二聚化活性。根据 PPI 网络鉴定出 8 个枢纽基因。基于 circRNAs 的生物学功能，获得了 3 个可能的 CAVD 疾病调控网络：hsa_circ_0026817-hsa-miR-211-5p-CACNA1C、hsa_circ_0007215-hsa-miR-1252-5p-MECP2 和 hsa_circ_0007215-hsa-miR-1343-3p-RBL1。
本生物信息学分析提示 circRNA-miRNA-mRNA 网络在 CAVD 发病机制中的功能作用，并为治疗提供了新的靶点。
