OBJECTIVE: To detect the differential expressions of miRNAs in left atrial appendage (LAA) in patients with atrial fibrillation (AF). METHODS: Left atrial samples were collected from nonvalvular AF patients and healthy controls. The miRNA transcriptome was analyzed by microarray and verified by real-time reverse transcription-polymerase chain reaction. Computational prediction identified the AF-related miRNAs and its target gene. In the meantime, construction of reporter plasmids and reporter assays were performed to test whether miRNA could represses the Luciferase activity of 3' untranslated regions of its target gene. RESULTS: MiR-155, miR-142-3p, miR-19b, miR-223, miR-146b-5p, miR-486-5p, miR-301b, miR-193b, miR-519b were found to be up-regulated by > 2 folds whereas miR-193a-5p was down-regulated. In particular, the level of miR-155 increased by 5.78 folds in AF patients versus healthy controls (9.42 ± 4.74 vs 1.63 ± 0.65). Furthermore, computational prediction identified CACNA1C encoding Cav1.2 as a direct target of miR-155. In the meantime, the construction of reporter plasmids and reporter assays showed that miR-155 repressed the Luciferase activity of 3' untranslated regions of CACNA1C. CONCLUSION: In LAA sample of nonvalvular AF, there is an expression of AF-related miRNAs including miR-155. And it reveals a potential link between the regulation of Cav1.2 and miR-155 in electric remodeling of AF.
OBJECTIVE: To detect the differential expressions of miRNAs in left atrial appendage (LAA) in patients with atrial fibrillation (AF). METHODS: Left atrial samples were collected from nonvalvular AFpatients and healthy controls. The miRNA transcriptome was analyzed by microarray and verified by real-time reverse transcription-polymerase chain reaction. Computational prediction identified the AF-related miRNAs and its target gene. In the meantime, construction of reporter plasmids and reporter assays were performed to test whether miRNA could represses the Luciferase activity of 3' untranslated regions of its target gene. RESULTS:MiR-155, miR-142-3p, miR-19b, miR-223, miR-146b-5p, miR-486-5p, miR-301b, miR-193b, miR-519b were found to be up-regulated by > 2 folds whereas miR-193a-5p was down-regulated. In particular, the level of miR-155 increased by 5.78 folds in AFpatients versus healthy controls (9.42 ± 4.74 vs 1.63 ± 0.65). Furthermore, computational prediction identified CACNA1C encoding Cav1.2 as a direct target of miR-155. In the meantime, the construction of reporter plasmids and reporter assays showed that miR-155 repressed the Luciferase activity of 3' untranslated regions of CACNA1C. CONCLUSION: In LAA sample of nonvalvular AF, there is an expression of AF-related miRNAs including miR-155. And it reveals a potential link between the regulation of Cav1.2 and miR-155 in electric remodeling of AF.
Authors: Frehiwet T Hailu; Anis Karimpour-Fard; Lee S Toni; Michael R Bristow; Shelley D Miyamoto; Brian L Stauffer; Carmen C Sucharov Journal: Pediatr Res Date: 2021-05-19 Impact factor: 3.953