title: Underexpression of CACNA1C Caused by Overexpression of microRNA-29a Underlies the Pathogenesis of Atrial Fibrillation.
abstract: BACKGROUND The objective of this study was to investigate the molecular mechanism of atrial fibrillation (AF), as well as the negative regulatory relationship between miR-29a-3p and CACNA1C. MATERIAL AND METHODS We searched the online miRNA database (www.mirdb.org) and identified the miR-29a-3p binding sequence within the 3'-UTR of the target gene, and then conducted luciferase assay to verify it. The cells were transfected with miR-29a-3p and ICa,L was determined in those cells. RESULTS We validated CACNA1C to be the direct target gene of miR-29a-3p. We also established the negative regulatory relationship between miR-29a-3p and CACNA1C via studying the relative luciferase activity. We also conducted real-time PCR and Western blot analysis to study the mRNA and protein expression level of CACNA1C among different groups of cells treated with scramble control, 30nM miR-29a-3p mimics, and 60nM miR-29a-3p mimics, indicating a negative regulatory relationship between miR-29a-3p and CACNA1C. We next analyzed whether miR-29a-3p transfection in cardiomyocytes produced the effects on the ICa,L induced by electrical remodeling, and found a tonic inhibition of IBa by endogenous miR-29a-3p in atrial myocytes. CONCLUSIONS We validated the negative regulation between miR-29a-3p and CACNA1C, and found that miR-29a-3p might a potential therapeutic target in the treatment of AF.
authors.affiliation: Department of Cardiovascular, No. 7 People's Hospital in Zhengzhou, Zhengzhou, Henan, China (mainland).
authors.forename: Yujie
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Cardiovascular, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China (mainland).
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Cardiovascular, No. 7 People's Hospital in Zhengzhou, Zhengzhou, Henan, China (mainland).
authors.forename: Chunguang
authors.initials: C
authors.lastname: Qiu
mesh_terms: D020413:3' Untranslated Regions; D001281:Atrial Fibrillation / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D020746:Calcium Channels, L-Type / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D015536:Down-Regulation; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger