The Role Of MicroRNA-155 Contributes To Atrial Remodeling In Human Atrial Fibrillation Regulated By Small Conductance Calcium Activated Potassium Channel 3

Background and Objective atrial fibrillation(AF)is one of the most common rapid atrial arrhythmias in clinical practice.Some studies have shown that,atrial electrical remodeling caused by changes of ion channels is one of the main mechanisms.small conductance calcium activated potassium channel3(SK3)is one of the subtypes of the small conductance calcium-activated potassium channels family.The highly expression of SK3 in atrial myocytes has been confirmed,and it plays a role in the repolarization of action potential duration in the cardiomycyte.The functional abnormalities of SK3 play an important role in the pathogenesis of AF.MicroRNAs are a class of endogenous non-coding small RNAs,which are highly conserved among differnt species.Bybinding to the 3'-untranslated region(3'-UTR)of the target genes mRNA,microRNAs regulate the expression of their target genes at the post-transcriptional levels.Studies have shown that,through regulating the expression of their ion channel targets,relatived microRNAs participate in atrial's electrical remodeling.However,previous studies focus on calcium channels and inward rectifier potassium channels,there is little research about the effect of SK3 in AF.Bioinformatics prediction shows that,KCNN3,which encodes SK3,is one of the taget genes regulated by microRNA-155(miR-155).MiR-155 play a role in cornary heart disease,hypertention,cardiac hypertrophy,heart failure and other cardiovascular diseases.Compared with sinus rhythm(SR),the up-regulation of miR-155 in atrial of patients with AF has been verified.We detected the expressions of the miR-155 and SK3 in the right atrial appendage tissue of patients with chronic AF.MiR-155 mimic or inhibitor were transfected into AC16 cells respectively to investigate the role of miR-155 in the reconstruction of SK3 in atrial of patients with chronic AF.Methods Right atrial appendages were obtained from 67 patients undergoing cardiac surgery,including 31 patients with chronic AF and 36 patients with SR.The expression level of miR-155 was determined by real-time quantitative PCR(RT-qPCR).The mRNA or protein levels of SK3 were determined by RT-qPCR or Western blot(WB),respectively.miR-155 mimic or miR-155 inhibitor were transfected into AC16 cells respectively to investigate the effects of miR-155 on SK3 in AC16 cells.Results The expression of miR-155 was found to be significantly up-regulated in AF patients compared with patients with SR(1.292±0.261vs0.310±0.161,P<0.01).No significant difference at the mRNA expression level of SK3 was found between patients with AF and patients withSR(0.855±0.295vs0.917±0.253,P>0.05),but the protein expression of SK3 in patients with AF was significantly lower than that of patients with SR(0.182±0.043vs0.302±0.064,P<0.01).There was a negative correlation between the expression level of miR-155 and the protein expression level of SK3 in right atrial appendage(r=-0.735,P<0.01).miR-155 mimic reduced the protein expression of SK3 in AC16 cells,while mi R-155 inhibitor incresed the protein expression of SK3,but both had no effect on the mRNA expression of SK3.Conclusion Upregulation of miR-155 may contribute to atrial electrical remodeling in human atrial fibrillation by targeting SK3.