YY1-induced upregulation of lncRNA KCNQ1OT1 regulates angiotensin II-induced atrial fibrillation by modulating miR-384b/CACNA1C axis

Biochem Biophys Res Commun. 2018 Oct 20;505(1):134-140. doi: 10.1016/j.bbrc.2018.09.064. Epub 2018 Sep 18.

Abstract

Recent years, the role of long non-coding RNAs (lncRNAs) in atrial fibrillation (AF) has been gradually elucidated. In the current study, we measured the expression of ten AF-related lncRNAs to do qRT-PCR analysis. LncRNA KCNQ1 overlapping transcript 1 (KCNQ1OT1) was found to be significantly upregulated in AF model and Ang-II-induced mice heart. CACNA1C has been reported as a biomarker in atrial fibrillation. Here, we found that the expression pattern of CACNA1C was consistent with that of KCNQ1OT1. Electrophysiological study was conducted to demonstrate the effect of KCNQ1OT1 and CACNA1C on the Effective refractory period (ERP), interatrial conduction time (IACT), incidence of AF and AF duration of Ang-II-induced mice heart. Mechanically, KCNQ1OT1 contributed to the upregulation of CACNA1C by binding with miR-384. Furthermore, YY1 could activate the transcription of KCNQ1OT1 and CACNA1C. In conclusion, the present study revealed that YY1-induced upregulation of lncRNA KCNQ1OT1 regulates angiotensin II-induced atrial fibrillation by regulating miR-384/CACNA1C axis.

Keywords: Atrial fibrillation; CACNA1C; KCNQ1OT1; YY1; miR-384.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II
  • Animals
  • Atrial Fibrillation / chemically induced
  • Atrial Fibrillation / genetics*
  • Atrial Fibrillation / physiopathology
  • Base Sequence
  • Calcium Channels, L-Type / genetics*
  • Calcium Channels, L-Type / metabolism
  • Cells, Cultured
  • Gene Expression Regulation*
  • HEK293 Cells
  • Humans
  • Male
  • Mice, Inbred C57BL
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • RNA Interference
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Sequence Homology, Nucleic Acid
  • Signal Transduction / genetics
  • Up-Regulation
  • YY1 Transcription Factor / genetics*
  • YY1 Transcription Factor / metabolism

Substances

  • CACNA1C protein, mouse
  • Calcium Channels, L-Type
  • KCNQ1OT1 RNA
  • MIRN384 microRNA, mouse
  • MicroRNAs
  • RNA, Long Noncoding
  • YY1 Transcription Factor
  • Angiotensin II