Qi Jie, Han Wenqi, Zhong Nier, Gou Qiling, Sun Chaofeng
Second Department of Cardiovascular Medicine, Shaanxi Provincial People's Hospital, Xi'an, 710068, People's Republic of China.
Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China.
Funct Integr Genomics. 2022 Dec 23;23(1):16. doi: 10.1007/s10142-022-00941-w.
Coronary heart disease is a cardiovascular disease with high morbidity and mortality. Although great progress has been made in treatment, the prognosis is still very poor. Therefore, this project aims to screen potential diagnostic markers and therapeutic targets related to the progression of coronary heart disease. A total of 94 overlapping differentially expressed mRNAs and 70 differentially expressed miRNAs were identified from GSE20681, GSE12288, GSE49823, and GSE105449. Through a series of bioinformatics methods and experiment, we obtained 5 core miRNA-mRNA regulatory pairs, and selected miR-338-3p/RPS23 for functional analysis. Moreover, we found that RPS23 directly targets miR-338-3p by dual luciferase assay, western, and qPCR. And the expression of miR-338-3p and RPS23 is negatively correlated. The AUC value of miR-338-3p is 0.847. Downregulation of miR-338-3p can significantly inhibit the proliferation and migration of HUVEC. On the contrary, overexpression of miR-338-3p promoted the proliferation and migration of HUVEC. In addition, the interference of RPS23 expression can reverse the regulation of miR-338-3p on HUVEC proliferation. In conclusion, miR-338-3p/RPS23 may be involved in the progression of coronary heart disease, and miR-338-3p may be a diagnostic biomarker and therapeutic target for coronary heart disease.
冠心病是一种发病率和死亡率都很高的心血管疾病。尽管在治疗方面已经取得了很大进展，但预后仍然很差。因此，本项目旨在筛选与冠心病进展相关的潜在诊断标志物和治疗靶点。从GSE20681、GSE12288、GSE49823和GSE105449中总共鉴定出94个重叠的差异表达mRNA和70个差异表达miRNA。通过一系列生物信息学方法和实验，我们获得了5个核心miRNA-mRNA调控对，并选择miR-338-3p/RPS23进行功能分析。此外，我们通过双荧光素酶检测、western印迹和qPCR发现RPS23直接靶向miR-338-3p。并且miR-338-3p和RPS23的表达呈负相关。miR-338-3p的AUC值为0.847。下调miR-338-3p可显著抑制人脐静脉内皮细胞（HUVEC）的增殖和迁移。相反，过表达miR-338-3p促进HUVEC的增殖和迁移。此外，干扰RPS23的表达可逆转miR-338-3p对HUVEC增殖的调控。总之，miR-338-3p/RPS23可能参与冠心病的进展，并且miR-338-3p可能是冠心病的诊断生物标志物和治疗靶点。
