Data_Sheet_1_miR-190a-5p Partially Represses the Abnormal Electrical Activity of SCN3B in Cardiac Arrhythmias by Downregulation of IL-2.zip
Cardiac arrhythmias (CAs) are generally caused by disruption of the cardiac conduction system; interleukin-2 (IL-2) is a key player in the pathological process of CAs. This study aimed to investigate the molecular mechanism underlying the regulation of IL-2 and the sodium channel current of sodium voltage-gated channel beta subunit 3 (SCN3B) by miR-190a-5p in the progression of CAs. ELISA results suggested the concentration of peripheral blood serum IL-2 in patients with atrial fibrillation (AF) to be increased compared to that in normal controls; fluorescence in situ hybridization indicated that the expression of IL-2 in the cardiac tissues of patients with AF to be upregulated and that miR-190a-5p to be downregulated. Luciferase reporter assay, quantitative real-time-PCR, and whole-cell patch-clamp experiments confirmed the downregulation of IL-2 by miR-190a-5p and influence of the latter on the sodium current of SCN3B. Overall, miR-190a-5p suppressed the increase in SCN3B sodium current caused by endogenous IL-2, whereas miR-190a-5p inhibitor significantly reversed this effect. IL-2 was demonstrated to be directly regulated by miR-190a-5p. We, therefore, concluded that the miR-190a-5p/IL-2/SCN3B pathway could be involved in the pathogenesis of CAs and miR-190a-5p might acts as a potential protective factor in pathogenesis of CAs.
History
References
- https://doi.org//10.4049/jimmunol.172.7.3983
- https://doi.org//10.1126/sciimmunol.aat1482
- https://doi.org//10.1097/00019501-200309000-00003
- https://doi.org//10.1378/chest.94.4.750
- https://doi.org//10.1016/j.cyto.2015.01.026
- https://doi.org//10.1093/europace/eup300
- https://doi.org//10.1177/2324709617749622
- https://doi.org//10.1002/cncr.10968
- https://doi.org//10.1016/j.jacep.2018.03.006
- https://doi.org//10.1016/j.pharmthera.2011.03.003
- https://doi.org//10.1016/j.hrthm.2007.03.040
- https://doi.org//10.3389/fphar.2017.00036
- https://doi.org//10.1186/s12872-015-0179-x
- https://doi.org//10.3892/etm.2020.8599
- https://doi.org//10.7554/eLife.05005
- https://doi.org//10.1074/jbc.M115.695080
- https://doi.org//10.1016/j.bbadis.2015.07.016
- https://doi.org//10.1016/j.jacc.2012.04.063
- https://doi.org//10.1186/s12935-019-0984-x
- https://doi.org//10.2147/OTT.S232848
- https://doi.org//10.1016/j.bbrc.2014.12.004
- https://doi.org//10.1186/s12943-018-0818-9
- https://doi.org//10.1002/jcp.28907
- https://doi.org//10.1152/ajplung.00146.2017
- https://doi.org//10.1016/j.bbadis.2016.11.018
- https://doi.org//10.1089/jir.2008.0082.2906
- https://doi.org//10.1093/cvr/cvq348
- https://doi.org//10.1093/cvr/cvp417
- https://doi.org//10.1253/circj.CJ-12-0995
- https://doi.org//10.1016/j.jacc.2008.02.068
- https://doi.org//10.1093/eurjhf/hfs191
- https://doi.org//10.1007/s00380-019-01492-0