Basic & Clinical Medicine ›› 2022, Vol. 42 ›› Issue (4): 590-598.doi: 10.16352/j.issn.1001-6325.2022.04.006

• Original Articles • Previous Articles     Next Articles

miRNAs may involve in ventricular septal defect through regulating the MAPK pathway

JIANG Hui, ZHANG Lin*   

  1. College of Life Sciences, Zhejiang Chinese Medicial University, Hangzhou 310053, China
  • Received:2021-04-25 Revised:2021-08-13 Online:2022-04-05 Published:2022-04-01
  • Contact: *

Abstract: Objective To investigate the role of miRNAs in pathogenesis of ventricular septal defect. Methods The miRNAs differential expression in whole blood samples from ventricular septal defect (VSD) group and normal group was analyzed by miRNAs expression microarray experiment and the target genes were predicted by biological information databases miRbase, Targetscan and Miranda. Target gene signaling pathways were screened through KEGG and REACTOME pathway databases, the transcription and protein expression of key genes in key signaling pathways were detected by RT-qPCR and Western blot. Results A total of 22 cases of differentially expressed miRNA were obtained in the experiment, and 12 744 target genes were predicted. A total of 126 pathways were found and the MAPK pathway, which was closely related to heart development, and was deeply analyzed. Among them, the transcription and protein expression of RASA1 and NF1 in ERK pathway were significantly increased (P<0.05), the transcription and protein expression of RAS were significantly decreased(P<0.05), and the expression levels of ERK and MEK1 phosphorylated proteins were also significantly decreased(P<0.05); the transcription and protein expression of TNF, TNFRSF1A and TRAF2 in the p38/MAPK sub-pathway were significantly increased(P<0.05), the expression of p38 phosphorylated proteins was significantly increased(P<0.05), The transcrip-tion, total protein and phosphorylated protein expression of MEF2C were significantly increased(P<0.05). The above pathways were found to be regulated by 12 miRNA. Conclusions The abnormal expression of 22 differentially expressed miRNAs leads to a variety of known cardiac development-related gene expression disorders. Among them, 12 abnormally expressed miRNAs inhibit the ERK pathway and thus inhibit the differentiation of cardiomyocytes and over-activate the expression of p38/MAPK pathway to promote the abnormal apoptosis of cardiomyocytes, and ultimately lead to the occurrence of VSD.

Key words: ventricular septal defect, differentially expressed miRNAs, MAPK pathway

CLC Number: