Department of Biosciences, COMSATS University Islamabad, Islamabad 45550, Pakistan.
Department of Biochemistry, Shifa College of Medicine, Shifa Tameer-e-Millat University, Islamabad 45550, Pakistan.
Genes (Basel). 2023 Feb 22;14(3):550. doi: 10.3390/genes14030550.
Coronary heart disease (CHD) is a global health concern, and its molecular origin is not fully elucidated. Dysregulation of ncRNAs has been linked to many metabolic and infectious diseases. This study aimed to explore the role of circRNAs in the pathogenesis of CHD and predicted a candidate circRNA that could be targeted for therapeutic approaches to the disease. circRNAs associated with CHD were identified and CHD gene expression profiles were obtained, and analyzed with GEO2R. In addition, differentially expressed miRNA target genes (miR-DEGs) were identified and subjected to functional enrichment analysis. Networks of circRNA/miRNA/mRNA and the miRNA/affected pathways were constructed. Furthermore, a miRNA/mRNA homology study was performed. We identified that hsa_circ_0126672 was strongly associated with the CHD pathology by competing for endogenous RNA (ceRNA) mechanisms. hsa_circ_0126672 characteristically sponges miR-145-5p, miR-186-5p, miR-548c-3p, miR-7-5p, miR-495-3p, miR-203a-3p, and miR-21. Up-regulation of has_circ_0126672 affected various CHD-related cellular functions, such as atherosclerosis, JAK/STAT, and Apelin signaling pathways. Our results also revealed a perfect and stable interaction for the hybrid of miR-145-5p with and . Finally, miR-145-5p had the highest degree of interaction with the validated small molecules. Henchashsa_circ_0126672 and target miRNAs, notably miR-145-5p, could be good candidates for the diagnosis and therapeutic approaches to CHD.
冠心病(CHD)是一个全球性的健康问题,其分子起源尚未完全阐明。ncRNAs 的失调与许多代谢和传染病有关。本研究旨在探讨 circRNAs 在 CHD 发病机制中的作用,并预测一种可能成为该疾病治疗方法的候选 circRNA。鉴定与 CHD 相关的 circRNAs,并获得 CHD 基因表达谱,然后使用 GEO2R 进行分析。此外,还鉴定了差异表达的 miRNA 靶基因(miR-DEGs),并进行了功能富集分析。构建了 circRNA/miRNA/mRNA 网络和 miRNA/受影响途径的网络。此外,还进行了 miRNA/mRNA 同源性研究。我们通过竞争内源性 RNA(ceRNA)机制发现 hsa_circ_0126672 与 CHD 病理密切相关。hsa_circ_0126672 特征性地吸附 miR-145-5p、miR-186-5p、miR-548c-3p、miR-7-5p、miR-495-3p、miR-203a-3p 和 miR-21。hsa_circ_0126672 的上调影响了各种与 CHD 相关的细胞功能,如动脉粥样硬化、JAK/STAT 和 Apelin 信号通路。我们的研究结果还揭示了 miR-145-5p 与 的杂交具有完美而稳定的相互作用。最后,miR-145-5p 与验证的小分子的相互作用程度最高。因此,hsa_circ_0126672 和靶 miRNAs,特别是 miR-145-5p,可能是 CHD 诊断和治疗方法的良好候选物。