Bioinformatics Prediction of miRNAs Regulating the Differentiation of Pluripotent Stem Cells Into Insulin-Producing Cells

Background and Aim: Nowadays, the cell type conversion is a newmethod for the generation of insulin-producing cells (IPCs) from otherdifferentiated or stem cells to treat diabetic patients. Identificationof the molecular mechanisms involved in the differentiation anddevelopment of IPCs is critical in the cell type conversion assays. Inthis regard, microRNAs (miRNAs) are important molecular tools, whichpost-transcriptionally regulate the expression of genes involved inIPCs differentiation and development. The present in silico study wasdesigned to analyze and identify the effective miRNAs that control thedifferentiation of pluripotent stem cells (PSCs) into IPCs.Methods: To do this, a list of 8 effective genes (Sox17, FoxA2, Pdx1,Nkx6.1, Ptf1a, Sox9, Ngn3, and Neurod1) that promote the differentiationof PSCs into IPCs was obtained from previous studies. All possiblemiRNAs, which target 3′-UTR of the selected genes, were separatelypredicted by using miRWalk and miRmap tools and then sorted basedon the miRNAs which target common sequences. Finally, the miRNAswhich target the greatest number of genes selected from the list.Results: The results of this in-silico analysis presented 3 possible miRNAs.These 3 miRNAs inhibited the expression of Sox17, FoxA2, Ptf1A, Sox9,and Neurod1 genes, which are important for the differentiation of PSCsinto IPCs. In this regard, it found that miR-3529 targeted Sox17, FoxA2,Ptf1A, and Sox9. Moreover, results indicated that miR-5011 inhibited theexpression of Ptf1A, Sox9, and Neurod1. Our results also showed thatmiR-4775 targeted Sox9, Pdx1, and Neurod1.Conclusion: In conclusion, the results of this in silico study provide aprospect to design experimental studies for examination of the genuineactivity of the identified miRNAs and their effects on the expression ofgenes that control the differentiation of PSCs into IPCs

Keywords:

Insulin-producing cell , Pluripotent stem cell , Differentiation , miRNA , Bioinformatics