Introduction: Diabetic kidney disease (DKD) is a major global cause of end-stage-kidney disease. In view of its ongoing risk of disease progression, the search for a better biomarkers and treatment led to the discovery of microRNAs which regulate gene expression post-translationally. Recently, we reported a trend of upregulation of miR-145-5p in sera of type 2 diabetic patients with macroalbuminuria in a selected Malaysian population, which concurred with previous in vivo and in vitro studies of DKD. In addition, miR-145 has been implicated as a tumour suppressor in various cancers. Methods: In this study, bioinformatics tools were utilized to predict the mRNA targets of miR-145-5p. Results: A total of 683 and 224 experimentally-validated mRNA targets of miR-145-5p were identified by Tarbase and miRTarbase, respectively. Eighty-six (86) commonly identified targets were submitted to Metascape and Enrichr for enrichment analysis. Bioinformatics analysis and literature search suggested that insulin receptor substrate 1 (IRS1) was the most promising target of miR-145-5p. Its associated Gene Ontology terms and pathways included insulin-like growth factor receptor signalling and Forkhead transcription factors (FOXO), respectively. Based on these analyses, the roles of IRS1 in DKD were proposed. Conclusion: As the kidneys are heterogenous in cell types and the mechanism of miRNA is cell-type-dependent, target prediction of miR-145-5p by bioinformatics analysis is particularly important in DKD, to improve the likelihood of a successful in vitro experimental verification in specific renal cell types. In addition, this study attempts to utilize bioinformatics studies, which is not widely done in DKD, as recently reported.
Introduction: Diabetic kidney disease (DKD) remains the leading cause of chronic kidney disease (CKD) worldwide. Current biomarkers and treatment still fall short at preventing its progression. In search for a better diagnostic or therapeutic target, much interest in microRNAs, which act as post-translational regulators of gene expression has emerged. An upregulation of miR-101-3p was identified in the sera of type 2 diabetic patients with macroalbuminuria in a selected Malaysian population by profiler RT-PCR array. Using bioinformatics tools, this study aimed to predict the mRNA targets of miR-101-3p. Given the scarcity of bioinformatics studies in DKD, this study also attempted to fill the gap. Methods: The mRNA targets were identified from two experimentally validated databases, namely Tarbase and MirTarBase. The commonly identified mRNA targets were submitted to Metascape and Enrichr bioinformatic tools. Results: A total of 2630 and 342 mRNA targets of miR-101-3p were identified by Tarbase and miRTarbase, respectively. One-hundred ninety-seven (197) mRNA targets were submitted for functional enrichment analysis. Our bioinformatics and bibliographical analyses suggested that ras-related C3 botulinum toxin substrate 1 (RAC1) and Ras-associated protein-1 b (RAP1b) were the most promising putative mRNA targets of miR-101-3p. The most enriched Gene Ontology term and pathway associated with these putative mRNA targets included Ras protein signal transduction and focal adhesion, respectively. Based on these analyses, their molecular mechanisms were proposed. Conclusion: Given the structural heterogeneity of the kidneys and cell type-dependent miRNA modulation, an in-silico target prediction of miR-101-3p increases the probability of a successful future in-vitro experimental verification.
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