环状RNA应用于心肌损伤治疗的新进展

doi:10.3969/j.issn.1674-8115.2026.03.014

上海交通大学学报（医学版） ›› 2026, Vol. 46 ›› Issue (3): 391-399.doi: 10.3969/j.issn.1674-8115.2026.03.014

• 综述 • 上一篇

环状RNA应用于心肌损伤治疗的新进展

张叶婷¹, 郑雨轩², 陶鹏杰¹, 周文琴³, 吕东潮¹()

^1.上海中医药大学中西医结合学院，上海 201203
^2.上海中医药大学中药学院，上海 201203
^3.上海大学医学院，上海 200122

收稿日期:2025-08-04 接受日期:2025-11-27 出版日期:2026-03-28 发布日期:2026-03-30
通讯作者: 吕东潮，青年研究员，博士；电子信箱：lu_dongchao@shutcm.edu.cn。
作者简介:第一联系人：为共同第一作者（co first-authors）.
基金资助:
国家自然科学基金(82400423);上海市浦江项目(23PJ1412200)

Overview of new advances in the treatment of myocardial injury with circular RNA

Zhang Yeting¹, Zheng Yuxuan², Tao Pengjie¹, Zhou Wenqin³, Lü Dongchao¹()

^1.School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
^2.School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
^3.School of Medicine, Shanghai University, Shanghai 200122, China

Received:2025-08-04 Accepted:2025-11-27 Online:2026-03-28 Published:2026-03-30
Contact: Lü Dongchao, E-mail: lu_dongchao@shutcm.edu.cn.
Supported by:
National Natural Science Foundation of China(82400423);Shanghai Pujiang Program(23PJ1412200)

摘要/Abstract

摘要：

心血管疾病作为全球性重大公共卫生问题，至今仍缺乏有效的治疗方法。环状RNA（circular RNA，circRNA）因其独特的环形结构而具有的稳定性，在心肌梗死、心肌缺血再灌注损伤、心力衰竭以及肿瘤治疗引发的心脏毒性等与心肌损伤相关的病症中，发挥着关键的调控作用。circRNA通过对细胞存活、炎症反应、氧化应激等关键分子信号通路的调节，影响着心肌损伤的发生与发展过程。不仅如此，circRNA作为生物标志物，在心血管疾病的早期诊断与预后评估方面也展现出一定的应用潜力。借助RNA技术，如circRNA模拟物系统与siRNA系统，对circRNA进行基因功能的增益与缺失调控，有助于深入阐明其保护心肌损伤的作用机制。该文系统综述了circRNA在心肌损伤治疗领域的最新研究进展，重点归纳了基于体外转录和工程化环化技术研发的circRNA药物在临床前研究中的应用策略，探讨了circRNA作为新型治疗靶点的潜在价值，为心血管疾病的治疗提供了新的思路与方向。

关键词: 环状RNA, 非编码RNA, RNA治疗, 心脏毒性, 心肌损伤, 体外转录RNA技术, 工程化环化技术

Abstract:

Cardiovascular disease is a major global public health issue, yet effective treatment methods are still lacking. Circular RNA, with its unique circular structure that confers remarkable stability, exhibits significant regulatory effects in myocardial infarction, myocardial ischemia reperfusion injury, heart failure, and cardiotoxicity induced by cancer treatment, all of which are associated with myocardial injury. Circular RNA influences the occurrence and development of myocardial injury by regulating key molecular signaling pathways, including cell survival, inflammatory responses, and oxidative stress. In addition, circular RNA, as a biomarker, shows certain application prospects in the early diagnosis and prognosis assessment of cardiovascular diseases. By using RNA technologies, including the circular RNA mimic system and the siRNA system, to regulate the gain and loss of circular RNA gene functions, the mechanisms by which circular RNA protects against myocardial injury can be further clarified. This paper systematically reviews the latest research progress of circular RNA in the field of myocardial injury treatment, focuses on summarizing the application strategies of circular RNA-based therapeutics developed through in vitro transcription and engineered circularization technologies in pre clinical research, explores the potential value of circular RNA as a novel therapeutic target, and provides new ideas and directions for the treatment of cardiovascular diseases.

Key words: circular RNA, non-coding RNA, RNA therapy, cardiotoxicity, myocardial injury, in vitro transcription RNA technology, engineered circularization technology

中图分类号:

R542.2

张叶婷, 郑雨轩, 陶鹏杰, 周文琴, 吕东潮. 环状RNA应用于心肌损伤治疗的新进展[J]. 上海交通大学学报（医学版）, 2026, 46(3): 391-399.

Zhang Yeting, Zheng Yuxuan, Tao Pengjie, Zhou Wenqin, Lü Dongchao. Overview of new advances in the treatment of myocardial injury with circular RNA[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026, 46(3): 391-399.

图/表 3

图1 circRNA在心肌损伤中的调控网络示意图

Fig 1 Schematic graph of the circRNA-mediated regulatory network in myocardial injury

图2 circRNA生物标志物从发现到应用的路线

Fig 2 Workflow of circRNA biomarker discovery and application

图3 工程化circRNA的常用技术手段示意

Fig 3 Schematic diagram of the commonly used techniques for engineering circRNA

参考文献 40

[1]	杜艳涛, 吴涛. 肿瘤与心力衰竭相关性研究进展[J]. 生命科学, 2022, 34(7): 790-805.
	Du Y T, Wu T. The research progression of the relationship between cancer and heart failure[J]. Chin Bull Life Sci, 2022, 34(7): 790-805.
[2]	Rinaldi S, Moroni E, Rozza R, et al. Frontiers and challenges of computing ncRNAs biogenesis, function and modulation[J]. J Chem Theory Comput, 2024, 20(3): 993-1018.
[3]	Sanger H L, Klotz G, Riesner D, et al. Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures[J]. Proc Natl Acad Sci U S A, 1976, 73(11): 3852-3856.
[4]	Memczak S, Jens M, Elefsinioti A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency[J]. Nature, 2013, 495(7441): 333-338.
[5]	Saaoud F, Drummer I V C, Shao Y, et al. Circular RNAs are a novel type of non-coding RNAs in ROS regulation, cardiovascular metabolic inflammations and cancers[J]. Pharmacol Ther, 2021, 220: 107715.
[6]	Wang Y Y, Zhang J, Yang Y C, et al. Circular RNAs in human diseases[J]. MedComm, 2024, 5(9): e699.
[7]	Aquino-Jarquin G. CircRNA knockdown based on antisense strategies[J]. Drug Discov Today, 2024, 29(8): 104066.
[8]	Wen Z J, Xin H, Wang Y C, et al. Emerging roles of circRNAs in the pathological process of myocardial infarction[J]. Mol Ther Nucleic Acids, 2021, 26: 828-848.
[9]	Xue J, Zhuang J L, Wang X Y, et al. Mechanisms and therapeutic strategies for myocardial ischemia-reperfusion injury in diabetic states[J]. ACS Pharmacol Transl Sci, 2024, 7(12): 3691-3717.
[10]	Gao X Q, Liu C Y, Zhang Y H, et al. The circRNA CNEACR regulates necroptosis of cardiomyocytes through Foxa2 suppression[J]. Cell Death Differ, 2022, 29(3): 527-539.
[11]	Thomson D W, Dinger M E. Endogenous microRNA sponges: evidence and controversy[J]. Nat Rev Genet, 2016, 17(5): 272-283.
[12]	Ye X M, Hang Y W, Lu Y, et al. CircRNA circ-NNT mediates myocardial ischemia/reperfusion injury through activating pyroptosis by sponging miR-33a-5p and regulating USP46 expression[J]. Cell Death Discov, 2021, 7(1): 370.
[13]	Denzler R, Agarwal V, Stefano J, et al. Assessing the CeRNA hypothesis with quantitative measurements of miRNA and target abundance[J]. Mol Cell, 2014, 54(5): 766-776.
[14]	Nielsen A F, Bindereif A, Bozzoni I, et al. Best practice standards for circular RNA research[J]. Nat Methods, 2022, 19(10): 1208-1220.
[15]	Xiao H W, Zhang M Y, Wu H, et al. CIRKIL exacerbates cardiac ischemia/reperfusion injury by interacting with Ku70[J]. Circ Res, 2022, 130(5): e3-e17.
[16]	Shan T K, Yang T T, Jing P, et al. Circular RNA IGF1R promotes cardiac repair via activating β-catenin signaling by interacting with DDX5 in mice after ischemic insults[J]. Research (Wash D C), 2024, 7: 0451.
[17]	Lu D C, Chatterjee S, Xiao K, et al. A circular RNA derived from the insulin receptor locus protects against doxorubicin-induced cardiotoxicity[J]. Eur Heart J, 2022, 43(42): 4496-4511.
[18]	Liu X, Wang Q W, Li X Y, et al. Fast degradation of MecciRNAs by SUPV3L1/ELAC2 provides a novel opportunity to tackle heart failure with exogenous M ecciRNA[J]. Circulation, 2025, 151(17): 1272-1290.
[19]	Chen L L, Wang W J, Zhao Y H, et al. Circular RNA CHACR is involved in the pathogenesis of cardiac hypertrophy[J]. Theranostics, 2025, 15(8): 3627-3642.
[20]	Neufeldt D, Schmidt A, Mohr E, et al. Circular RNA circZFPM2 regulates cardiomyocyte hypertrophy and survival[J]. Basic Res Cardiol, 2024, 119(4): 613-632.
[21]	Joghataie P, Ardakani M B, Sabernia N, et al. The role of circular RNA in the pathogenesis of chemotherapy-induced cardiotoxicity in cancer patients: focus on the pathogenesis and future perspective[J]. Cardiovasc Toxicol, 2024, 24(11): 1151-1167.
[22]	Fang S W, Ainsworth T, Zhang P P. Circular RNAs as regulatory mediators and therapeutic targets in doxorubicin-induced cardiotoxicity[J]. Curr Probl Cardiol, 2025, 50(9): 103106.
[23]	Du W W, Yang W N, Chen Y, et al. Foxo3 circular RNA promotes cardiac senescence by modulating multiple factors associated with stress and senescence responses[J]. Eur Heart J, 2017, 38(18): 1402-1412.
[24]	Yu P J, Wang J Q, Xu G E, et al. RNA m6A-regulated circ-ZNF609 suppression ameliorates doxorubicin-induced cardiotoxicity by Upregulating FTO[J]. JACC Basic Transl Sci, 2023, 8(6): 677-698.
[25]	Han D, Wang Y J, Wang Y B, et al. The tumor-suppressive human circular RNA CircITCH sponges miR-330-5p to ameliorate doxorubicin-induced cardiotoxicity through upregulating SIRT6, survivin, and SERCA2a[J]. Circ Res, 2020, 127(4): e108-e125.
[26]	Vasan R S. Biomarkers of cardiovascular disease: molecular basis and practical considerations[J]. Circulation, 2006, 113(19): 2335-2362.
[27]	Madè A, Bibi A, Garcia-Manteiga J M, et al. circRNA-miRNA-mRNA deregulated network in ischemic heart failure patients[J]. Cells, 2023, 12(21): 2578.
[28]	Wang L Y, Shen C, Wang Y Y, et al. Identification of circular RNA Hsa_circ_0001879 and Hsa_circ_0004104 as novel biomarkers for coronary artery disease[J]. Atherosclerosis, 2019, 286: 88-96.
[29]	Vausort M, Salgado-Somoza A, Zhang L, et al. Myocardial infarction-associated circular RNA predicting left ventricular dysfunction[J]. J Am Coll Cardiol, 2016, 68(11): 1247-1248.
[30]	Liu X Y, Zhang Y P, Yuan W, et al. Exosomal CircRNAs in circulation serve as diagnostic biomarkers for acute myocardial infarction[J]. Front Biosci (Landmark Ed), 2024, 29(4): 149.
[31]	Zhou Q L, Boeckel J N, Yao J H, et al. Diagnosis of acute myocardial infarction using a combination of circulating circular RNA cZNF292 and clinical information based on machine learning[J]. MedComm, 2023, 4(3): e299.
[32]	Schulte C, Barwari T, Joshi A, et al. Comparative analysis of circulating noncoding RNAs versus protein biomarkers in the detection of myocardial injury[J]. Circ Res, 2019, 125(3): 328-340.
[33]	Jiao J, Gao T, Shi H, et al. A method to directly assay circRNA in real samples[J]. Chem Commun, 2018, 54(95): 13451-13454.
[34]	Zhou Q L, Zhang Z R, Bei Y H, et al. Circular RNAs as novel biomarkers for cardiovascular diseases[J]. Adv Exp Med Biol, 2018, 1087: 159-170.
[35]	Kishore R, Garikipati V N S, Gonzalez C. Role of circular RNAs in cardiovascular disease[J]. J Cardiovasc Pharmacol, 2020, 76(2): 128-137.
[36]	Lu D C, Cushman S, Thum T, et al. Gene therapy and cardiovascular diseases[J]. Adv Exp Med Biol, 2023, 1396: 235-254.
[37]	Zhang Z Y, Fu Y L, Ju X L, et al. Advances in engineering circular RNA vaccines[J]. Pathogens, 2024, 13(8): 692.
[38]	Liu C X, Guo S K, Nan F, et al. RNA circles with minimized immunogenicity as potent PKR inhibitors[J]. Mol Cell, 2022, 82(2): 420-434.e6.
[39]	Wesselhoeft R A, Kowalski P S, Anderson D G. Engineering circular RNA for potent and stable translation in eukaryotic cells[J]. Nat Commun, 2018, 9(1): 2629.
[40]	国家药品监督管理局药品审评中心。上海环码生物医药有限公司HM2002注射液临床试验受理公示[EB/OL]. (2025-01-10)[2025-10-31]. https://www.cde.org.cn.
	Center for Drug Evaluation, National Medical Products Administration. Clinical trial application announcement of hm2002 injection by shanghai huanma biomedical Co, Ltd. [EB/OL]. (2025-01-10) [2025-10-31]. https:// www.cde.org.cn.

环状RNA应用于心肌损伤治疗的新进展

Overview of new advances in the treatment of myocardial injury with circular RNA

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