4.6 Article

MiR-486-3p and MiR-938-Important Inhibitors of Pacemaking Ion Channels and/or Markers of Immune Cells

Journal

APPLIED SCIENCES-BASEL
Volume 11, Issue 23, Pages -

Publisher

MDPI
DOI: 10.3390/app112311366

Keywords

miR-486-3p; miR-938; Ca(v)1; 3; Ca(v)3; 1; TPSAB1; sinus node; pacemaking channels; mast cells; cardiovascular diseases

Funding

  1. BRITISH HEART FOUNDATION [FS/17/67/33483]
  2. Leducq Foundation (THE FANTACY ) [19CVD03]

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The study confirmed that miR-486-3p significantly downregulates Ca(v)1.3, Ca(v)3.1, and TPSAB1-mediated luciferase activity, while miR-938 only significantly downregulates TPSAB1-mediated luciferase activity. This suggests that miR-486-3p could be a potential therapeutic target for treating sinus node dysfunctions.
The sinus node (SN) is the heart's primary pacemaker and has a unique expression of pacemaking ion channels and immune cell markers. The role of microribonucleic acids (miRNAs) in control of ion channels and immune function of the sinus node is not well understood. We have recently shown that hsa-miR-486-3p downregulates the main pacemaking channel HCN4 in the SN. In addition, we recently demonstrated that immune cells are significantly more abundant in the SN compared to the right atrium. The aim of this study was to validate the previously predicted interactions between miRNAs and mRNAs of key Ca2+ ion channels (involved in peacemaking) and mRNA of TPSAB1-(a mast cells marker) using luciferase assay. We now show that miR-486 significantly downregulates Ca(v)1.3, Ca(v)3.1, and TPSAB1-mediated luciferase activity, while miR-938 significantly downregulates only TPSAB1-mediated luciferase activity. This makes miR-486-3p a potential therapeutic target in the treatment of SN dysfunctions.

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