Comprehensive functional and profiling analysis of circular RNAs in type 2 diabetes mellitus: unveiling novel and biomarker therapeutic targets

Insulin failures cause excessive blood sugar levels in people with diabetes mellitus, a metabolic disorder. CircRNAs, covalently bonded closed RNA molecules, were first discovered in 1976 and 1979 in human HeLa cells. They play a crucial role in diabetes mellitus progression, demonstrating their potential as biomarkers and therapeutics. This work aims to identify the key genes and related circRNAs linked to diabetes and their possible therapeutic applications. A total of seven datasets were downloaded, out of which four datasets from the GEO database, i.e., GSE114248, GSE182737, GSE206041, and GSE209612, contain 1,404 differentially expressed circRNAs linked with diabetes mellitus. The obtained datasets were analyzed through GEO2R. For functional enrichment analysis database named DAVID has been used. The next step was to use STRING for PPIs, which were then visualized using Cytoscape. The MCC technique was used to locate hub genes. The hub genes were RPS6, RACK1, RPL18A, RPLP0, MED1, CD74, EEF2, RPL39, HABP4 and BUB1B. The 4 potential proteins of these hub genes, i.e., Hyaluronic Acid-binding protein 4, Budding uninhibited by benzimidazoles 1 homolog beta, Ribosomal protein L18A and Ribosomal protein L39, were then docked using PyRx with nine different ligands that can be potentially used as therapeutics in diabetes. The study revealed that Benfotiamine, Gliquidone, Metahexamide, Troglitazone and Rivoglitazone are the most suitable ligands that can be used as therapeutics in diabetes mellitus.