关键词: 永久性房颤, microRNA, mRNA, 靶基因, 网络调控

Abstract: Objectives: To screen for the atrial fibrillation related miRNAs and their target gene. to research the pathogenesis of permanent AF. Methods: Left atrium miRNA and mRNA profiling in patients with permanent AF (n=7) were compared with healthy heart donors in sinus rhythm (n=4) using microarrays. By predicting potential miRNA targets and making negative correlation analysis with differentially expressed mRNA, miRNA-target gene regulatory network was established. and key miRNA their target genes related with permanent AF were found, and qRT-PCR analysis were used to validated the expression of key miRNAs and gene in the network in another cohort. Bioinformatics analyses were performed to understanding the global regulating roles of miRNAs-gene network. Results: 610 mRNAs (fold change>2, P<0.05) were shown to be significantly changed in permanent AF patients compared with healthy controls. The target prediction and negative correlations analyses with the mRNA array have identified 20 dysregulated miRNAs and their 107 target genes. The corresponding miRNA-gene regulatory network were established. The miRNAs including miR-144, miR-1284, miR-1827, miR-1, miR-3613-3p and miR-101 and target genes containing CACNB2, EFNB1, PTEN, TAOK1, RUNX1 and TPM3 were found to be in the central part of the network.Some of their expression were further verified by qRT-PCR analysis on another cohort. Conclusions: Through the analysis of gene expression profile chip and miRNAs chip joint small sample of pAF left atrial tissue samples, establishing the miRNA-gene network, found that the pathogenesis of pAF important micrornas - target gene regulation and function, the result is more accurate.

Key words: atrial fibrillation, microRNA, mRNA, target gene, network