Significance of microRNA-targeted ErbB signaling pathway genes in cardiomyocyte differentiation

• Published in: Molecular and cellular probes Vol. 69; p. 101912
• Main Authors: Gholipour, Akram, Zahedmehr, Ali, Shakerian, Farshad, Irani, Shiva, Oveisee, Maziar, Mowla, Seyed Javad, Malakootian, Mahshid
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-06-2023; Elsevier
• Subjects: Cardiomyocyte differentiation; Cell Differentiation - genetics; Development; Differentially expressed miRNAs; ErbB signaling pathway; Gene Expression Profiling; Gene Expression Regulation; MicroRNAs - genetics; MicroRNAs - metabolism; Myocytes, Cardiac - metabolism; Signal Transduction - genetics; Small RNA-Sequencing; Development; ErbB signaling pathway; Small RNA-Sequencing; Cardiomyocyte differentiation; Differentially expressed miRNAs
• ISSN: 0890-8508; 1096-1194
• DOI: 10.1016/j.mcp.2023.101912

Cardiomyocyte differentiation is a complex process that follows the progression of gene expression alterations. The ErbB signaling pathway is necessary for various stages of cardiac development. We aimed to identify potential microRNAs targeting the ErbB signaling pathway genes by in silico approaches.
Small RNA-sequencing data were obtained from GSE108021 for cardiomyocyte differentiation. Differentially expressed miRNAs were acquired via the DESeq2 package. Signaling pathways and gene ontology processes for the identified miRNAs were determined and the targeted genes of those miRNAs affecting the ErbB signaling pathway were determined.
Results revealed highly differentially expressed miRNAs were common between the differentiation stages and they targeted the genes involved in the ErbB signaling pathway as follows: let-7g-5p targets both CDKN1A and NRAS, while let-7c-5p and let-7d-5p hit CDKN1A and NRAS exclusively. let-7 family members targeted MAPK8 and ABL2. GSK3B was targeted by miR-199a-5p and miR-214-3p, and ERBB4 was targeted by miR-199b-3p and miR-653-5p. miR-214-3p, miR-199b-3p, miR-1277-5p, miR-21-5p, and miR-21-3p targeted CBL, mTOR, Jun, JNKK, and GRB1, respectively. MAPK8 was targeted by miR-214-3p, and ABL2 was targeted by miR-125b-5p and miR-1277-5p, too.
We determined miRNAs and their target genes in the ErbB signaling pathway in cardiomyocyte development and consequently heart pathophysiology progression.
•ErbB signaling pathway, as one of the important pathways for maintenance and function of adult cardiomyocytes.•Several miRNAs underwent the most changes in expression along the differentiation transitions.•miRNAs: miR-653-5p, let-7c-5p, let-7d-5p, let-7g-5p, miR-1277-5p, miR-214-3p, miR-199a-5p, miR-125b-5p, miR-199b-3p, and miR-21-3p/5p.•Mentioned miRNAs have been targeted genes of ErbB signaling pathway including ABL2, MAPK8, CDKN1A, NRAS, GSK3B, ERBB4, mTOR, CBL, Jun, JNKK and GRB1.