Bioinformatically predicted miRNAs regulate the expression of TTN and MYBPC۳ genes

Background and Aim: MicroRNAs are a class of conserved non-coding RNAs which play a wide-ranging role in the regulation of eukaryotic gene expression at the post-transcriptional level by targeting the ۳′-untranslated region of mRNA sequences. TTN and MyBPC۳ genes play important roles in cardiac muscle contraction and muscle filament sliding. Finding the microRNAs which regulates cardiac genes post transcriptionally may help to understand the molecular mechanisms of the cardiovascular diseases. Through comprehensive bioinformatics methods, the present study aimed to predict the microRNAs which can target and hence regulate TTN and MyBPC۳ expression. Methods: Three bioinformatics databases including UCSC, mircode and miRWALK were utilized to predict the potential miRNAs that targeted ۳' UTR of TTN and MyBPC۳ genes. In addition, GTEx portal database was used to obtain expression of them in tissue. In addition, pathway enrichment analysis and Gene Oncology (GO) were accomplished by mirPath v.۳ database.Results: As expected, the expression profile of TTN and MYBPC۳ gene in UCSC shows that TTN and MyBPC۳ have high expression in the left ventricle of heart and atrial appendage. Based on mirWALK database analysis, ۹۴۲ miRNAs and ۸۰ miRNAs targeted TTN and MYBPC۳ genes, respectively (with ≥ ۵). Among them, we introduced miR-۴۵۱, miR-۴۹۲, miR-۶۰۷, miR-۱۴۴ and miR-۱۳۲۳ which can probably target the ۳'UTR of TTN and miR-۴۸۴, miR-۱۳۰۴-۵p, miR-۱۲۳۳-۳p, miR-۲۰۵/۲۰۵ab and miR-۵۰۵-۵p can possibly target MYBPC۳ as common miRNAs in all three surveyed databases. Furthermore, pathway analysis and Gene Oncology depicted that these miRNAs are involved in: Fatty acid biosynthesis, Arrhythmogenic right ventricular cardiomyopathy (ARVC), small molecule metabolic process, response to stress, blood coagulation and platelet activation.Conclusion: The discovery of microRNAs (miRNAs) has opened a whole new area of investigation in diagnostics and therapeutics for cardiovascular diseases. However, laboratory analyzes are required to confirm the candidate ones. Identification of the miRNAs which are regulate the expression of genes involved in cardiac tissues could help us to find the molecular mechanisms of the various type of cardiovascular diseases like cardiomyopathies.

Keywords:

TTN , MYBPC۳ , miR-۱۳۲۳ , miR-۵۰۵-۵p , Dilated cardiomyopathy.