nach oben

Journal of Cardiovascular Translational Research

Erschienen in:

07.02.2022 | Original Article

circCELF1 Inhibits Myocardial Fibrosis by Regulating the Expression of DKK2 Through FTO/m⁶A and miR-636

verfasst von: Xue-xun Li, Bin Mu, Xi Li, Zi-dong Bie

Erschienen in: Journal of Cardiovascular Translational Research | Ausgabe 5/2022

Einloggen, um Zugang zu erhalten

Abstract

The aim of this study is to explore the role of circCELF1/miR-636/DKK2 pathway in myocardial fibrosis (MF). RT-qPCR and western blot were used to detect the expression of circCELF1, miR-636, and DKK2 in activated cardiac fibroblasts (CFs) and the hearts of acute myocardial infarction (AMI) mice. The m⁶A level of DKK2 was detected by RIP and RT-qPCR. The regulation of circCELF1/miR-636/DKK2 pathway on CF viability, activation, apoptosis, and migration was verified by CCK-8, western blot, flow cytometry, and Transwell. Ang II induced downregulation of circCELF1 expression, while circCELF1 enhanced the expression of DKK2 by adsorbing miR-636. circCELF1 also reduced DKK2 m⁶A level by upregulating FTO expression, thereby inhibiting the binding of miR-636 to DKK2 and promoting DKK2 expression. Ang II promoted CF viability, activation, and migration through the circCELF1/miR-636/DKK2 pathway. Both miR-636 inhibitors and DKK2 effectively reduced MF and improved cardiac function in AMI mice.

Graphical abstract

Mannucci, P. M., Lotta, L. A., & Peyvandi, F. (2010). Genome-wide association studies in myocardial infarction and coronary artery disease. Journal of Tehran University Heart Center, 5, 116–121.PubMedPubMedCentral

Gronda, E., Sacchi, S., Benincasa, G., et al. (2019). Unresolved issues in left ventricular postischemic remodeling and progression to heart failure. Journal of Cardiovascular Medicine (Hagerstown, Md.), 20, 640–649. https://doi.org/10.2459/JCM.0000000000000834CrossRef

Frangogiannis NG (2020) Cardiac fibrosis. Cardiovasc Res:cvaa324. https://doi.org/10.1093/cvr/cvaa324

Bayoumi, A. S., Aonuma, T., Teoh, J. P., et al. (2018). Circular noncoding RNAs as potential therapies and circulating biomarkers for cardiovascular diseases. Acta Pharmacologica Sinica, 39, 1100–1109. https://doi.org/10.1038/aps.2017.196CrossRefPubMedPubMedCentral

Gu, X., Jiang, Y. N., Wang, W. J., et al. (2020). Comprehensive circRNA expression profile and construction of circRNA-related ceRNA network in cardiac fibrosis. Biomedicine & Pharmacotherapy, 125, 109944. https://doi.org/10.1016/j.biopha.2020.109944CrossRef

Yin, L., Tang, Y., & Jiang, M. (2020). Research on the circular RNA bioinformatics in patients with acute myocardial infarction. Journal of Clinical Laboratory Analysis, 35, e23621. https://doi.org/10.1002/jcla.23621CrossRefPubMedPubMedCentral

Lin, F., Yang, Y., Guo, Q., et al. (2020). Analysis of the molecular mechanism of acute coronary syndrome based on circRNA-miRNA network regulation. Evid Based Complement Alternat Med, 2020, 1584052. https://doi.org/10.1155/2020/1584052CrossRefPubMedPubMedCentral

Miyamoto, S. D., Karimpour-Fard, A., Peterson, V., et al. (2015). Circulating microRNA as a biomarker for recovery in pediatric dilated cardiomyopathy. Journal of Heart and Lung Transplantation, 34, 724–733. https://doi.org/10.1016/j.healun.2015.01.979CrossRef

Bardin, P., Foussignière, T., Rousselet, N., et al. (2019). miR-636: A newly-identified actor for the regulation of pulmonary inflammation in cystic fibrosis. Frontiers in Immunology, 10, 2643. https://doi.org/10.3389/fimmu.2019.02643CrossRefPubMedPubMedCentral

10.

Sun, L. Y., Bie, Z. D., Zhang, C. H., et al. (2016). MiR-154 directly suppresses DKK2 to activate Wnt signaling pathway and enhance activation of cardiac fibroblasts. Cell Biology International, 40, 1271–1279. https://doi.org/10.1002/cbin.10655CrossRefPubMed

11.

Liu, X. M., & Zhou, J. (2021). Multifaceted regulation of translation by the epitranscriptomic modification N6-methyladenosine. Critical Reviews in Biochemistry and Molecular Biology, 56, 137–148. https://doi.org/10.1080/10409238.2020.1869174CrossRefPubMed

12.

Qin, Y., Li, L., Luo, E., et al. (2020). Role of m6A RNA methylation in cardiovascular disease (Review). International Journal of Molecular Medicine, 46, 1958–1972. https://doi.org/10.3892/ijmm.2020.4746CrossRefPubMedPubMedCentral

13.

Mathiyalagan, P., Adamiak, M., Mayourian, J., et al. (2019). FTO-dependent N6-methyladenosine regulates cardiac function during remodeling and repair. Circulation, 139, 518–532. https://doi.org/10.1111/jcmm.13185CrossRefPubMedPubMedCentral

14.

Zhang, X., Xu, Y., Qian, Z., et al. (2018). circRNA_104075 stimulates YAP-dependent tumorigenesis through the regulation of HNF4a and may serve as a diagnostic marker in hepatocellular carcinoma. Cell Death & Disease, 9, 1091. https://doi.org/10.1038/s41419-018-1132-6CrossRef

15.

Li, X., Xue, X., Sun, Y., et al. (2019). MicroRNA-326-5p enhances therapeutic potential of endothelial progenitor cells for myocardial infarction. Stem Cell Research & Therapy, 10, 323. https://doi.org/10.1186/s13287-019-1413-8CrossRef

16.

Zeng, Y., Du, W. W., Wu, Y., et al. (2017). A circular RNA binds to and activates AKT phosphorylation and nuclear localization reducing apoptosis and enhancing cardiac repair. Theranostics, 7, 3842–3855. https://doi.org/10.1161/CIRCULATIONAHA.118.036146CrossRefPubMedPubMedCentral

17.

Zhou, B., & Yu, J. W. (2017). A novel identified circular RNA, circRNA_010567, promotes myocardial fibrosis via suppressing miR-141 by targeting TGF-β1. Biochemical and Biophysical Research Communications, 487, 769–775. https://doi.org/10.7150/thno.19764CrossRefPubMed

18.

Zhu, Y., Pan, W., Yang, T., et al. (2019). Upregulation of circular RNA CircNFIB attenuates cardiac fibrosis by sponging miR-433. Frontiers in Genetics, 10, 564. https://doi.org/10.1161/CIRCULATIONAHA.118.033794CrossRefPubMedPubMedCentral

19.

Salem, A. M., Ragheb, A. S., Hegazy, M. G. A., et al. (2019). Caffeic acid modulates miR-636 expression in diabetic nephropathy Rats. Indian Journal of Clinical Biochemistry, 34, 296–303. https://doi.org/10.1016/j.bbrc.2017.04.044CrossRefPubMed

20.

Ji, J., Xu, Q., He, X., et al. (2020). MicroRNA microarray analysis to detect biomarkers of aortic dissection from paraffin-embedded tissue samples. Interactive Cardiovascular and Thoracic Surgery, 31, 239–247. https://doi.org/10.3389/fgene.2019.00564CrossRefPubMed

21.

Morishita, A., Yoneyama, H., Iwama, H., et al. (2018). Circulating microRNA-636 is associated with the elimination of hepatitis C virus by ombitasvir/paritaprevir/ritonavir. Oncotarget, 9, 32054–32062. https://doi.org/10.1007/s12291-018-0743-0CrossRefPubMedPubMedCentral

22.

Yanagida, A., Iwaisako, K., Hatano, E., et al. (2011). Downregulation of the Wnt antagonist Dkk2 links the loss of Sept4 and myofibroblastic transformation of hepatic stellate cells. Biochimica et Biophysica Acta, 1812, 1403–1411. https://doi.org/10.1093/icvts/ivaa093CrossRefPubMed

23.

Hong, F., Hong, J., Wang, L., et al. (2015). Chronic exposure to nanoparticulate TiO2 causes renal fibrosis involving activation of the Wnt pathway in mouse kidney. Journal of Agricultural and Food Chemistry, 63, 1639–47. https://doi.org/10.18632/oncotarget.25889CrossRefPubMed

24.

Dorn, L. E., Lasman, L., Chen, J., et al. (2019). The N6-methyladenosine mRNA methylase METTL3 controls cardiac homeostasis and hypertrophy. Circulation, 139, 533–545. https://doi.org/10.1016/j.bbadis.2011.06.015CrossRefPubMed

Titel: circCELF1 Inhibits Myocardial Fibrosis by Regulating the Expression of DKK2 Through FTO/m6A and miR-636
verfasst von: Xue-xun Li
Bin Mu
Xi Li
Zi-dong Bie
Publikationsdatum: 07.02.2022
Verlag: Springer US
Erschienen in: Journal of Cardiovascular Translational Research / Ausgabe 5/2022
Print ISSN: 1937-5387
Elektronische ISSN: 1937-5395
DOI: https://doi.org/10.1007/s12265-022-10209-0

Neu im Fachgebiet Kardiologie

Ein Drittel der jungen Ärztinnen und Ärzte erwägt abzuwandern

07.05.2024 Medizinstudium Nachrichten

Extreme Arbeitsverdichtung und kaum Supervision: Dr. Andrea Martini, Sprecherin des Bündnisses Junge Ärztinnen und Ärzte (BJÄ) über den Frust des ärztlichen Nachwuchses und die Vorteile des Rucksack-Modells.

Vorhofflimmern bei Jüngeren gefährlicher als gedacht

06.05.2024 Vorhofflimmern Nachrichten

Immer mehr jüngere Menschen leiden unter Vorhofflimmern. Betroffene unter 65 Jahren haben viele Risikofaktoren und ein signifikant erhöhtes Sterberisiko verglichen mit Gleichaltrigen ohne die Erkrankung.

Chronisches Koronarsyndrom: Gefahr von Hospitalisierung wegen Herzinsuffizienz

06.05.2024 Herzinsuffizienz Nachrichten

Obwohl ein rezidivierender Herzinfarkt bei chronischem Koronarsyndrom wahrscheinlich die Hauptsorge sowohl der Patienten als auch der Ärzte ist, sind andere Ereignisse womöglich gefährlicher. Laut einer französischen Studie stellt eine Hospitalisation wegen Herzinsuffizienz eine größere Gefahr dar.

Das Risiko für Vorhofflimmern in der Bevölkerung steigt

02.05.2024 Vorhofflimmern Nachrichten

Das Risiko, im Lauf des Lebens an Vorhofflimmern zu erkranken, ist in den vergangenen 20 Jahren gestiegen: Laut dänischen Zahlen wird es drei von zehn Personen treffen. Das hat Folgen weit über die Schlaganfallgefährdung hinaus.

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Graphical abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 5/2022

Electroacupuncture at PC6 (Neiguan) Attenuates Angina Pectoris in Rats with Myocardial Ischemia–Reperfusion Injury Through Regulating the Alternative Splicing of the Major Inhibitory Neurotransmitter Receptor GABRG2

Distal Transradial Access: a Safe and Feasible Approach for Coronary Catheterization in Cases of Total Radial Artery Occlusion

The Mechanism Underlying the Regulation of LncRNA-ASLNC18810 Involved in the Abnormal Function of Vascular Endothelial Cell in Atherosclerosis: Its Function as a microRNA (miRNA) Sponge for miR-559

Fluid Shear Stress Ameliorates Prehypertension-Associated Decline in Endothelium-Reparative Potential of Early Endothelial Progenitor Cells

The Role of Angiogenesis and Arteriogenesisin Myocardial Infarction and Coronary Revascularization