Luo Mingyao, Du Mingyuan, Shu Chang, Liu Sheng, Li Jiehua, Zhang Lei, Li Xin
State Key Laboratory of Cardiovascular Diseases, Center of Vascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Department of Vascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.
Front Pharmacol. 2021 Oct 19;12:743945. doi: 10.3389/fphar.2021.743945. eCollection 2021.
Pulmonary embolism (PE) is a common pathologic condition that frequently occurs in patients with deep venous thrombosis. Severe PE may critically suppress cardiopulmonary function, thereby threatening the life of patients. Chronic pulmonary hypertension caused by PE may lead to deterioration of respiratory dysfunction, resulting in complete disability. MicroRNAs (miRNAs) are a group of abundantly expressed non-coding RNAs that exert multiple functions in regulating the transcriptome post-transcriptional targeting of mRNAs. Specifically, miRNAs bind to target mRNAs in a matching mechanism between the miRNA seed sequence and mRNA 3' UTR, thus modulating the transcript stability or subsequent translation activity by RNA-induced silencing complex. Current studies have reported the function of miRNAs as biomarkers of PE, revealing their mechanism, function, and targetome in venous thrombophilia. This review summarizes the literature on miRNA functions and downstream mechanisms in PE. We conclude that various related miRNAs play important roles in PE and have great potential as treatment targets. For clinical application, we propose that miRNA biomarkers combined with traditional biomarkers or miRNA signatures generated from microchips may serve as a great predictive tool for PE occurrence and prognosis. Further, therapies targeting miRNAs or their upstream/downstream molecules need to be developed more quickly to keep up with the progress of routine treatments, such as anticoagulation, thrombolysis, or surgery.
肺栓塞(PE)是一种常见的病理状况,常发生于深静脉血栓形成的患者中。严重的肺栓塞可能会严重抑制心肺功能,从而威胁患者生命。由肺栓塞引起的慢性肺动脉高压可能导致呼吸功能障碍恶化,进而导致完全残疾。微小RNA(miRNA)是一组大量表达的非编码RNA,在调节mRNA转录组的转录后靶向中发挥多种功能。具体而言,miRNA通过miRNA种子序列与mRNA 3'UTR之间的匹配机制与靶mRNA结合,从而通过RNA诱导沉默复合体调节转录稳定性或后续翻译活性。目前的研究报道了miRNA作为肺栓塞生物标志物的功能,揭示了它们在静脉血栓形成倾向中的机制、功能和靶标组。本综述总结了关于肺栓塞中miRNA功能和下游机制的文献。我们得出结论,各种相关miRNA在肺栓塞中发挥重要作用,并且作为治疗靶点具有巨大潜力。对于临床应用,我们建议将miRNA生物标志物与传统生物标志物相结合或由微芯片产生的miRNA特征可作为肺栓塞发生和预后的良好预测工具。此外,需要更快地开发针对miRNA或其上游/下游分子的疗法,以跟上常规治疗(如抗凝、溶栓或手术)的进展。