CircRNA-mediated ceRNA regulatory networks: transcriptomic insights into obesity type 2 diabetes progression and treatment strategies.

To investigate the pathogenesis of diabetes and identify novel biomarkers, we analyzed circRNA and mRNA expression profiles in serum samples from obese diabetic patients (O-T2DM) using high-throughput RNA sequencing. Our results showed that 442 differentially expressed circRNAs (343 up-regulated and 99 down-regulated) and 2756 differentially expressed mRNAs (277 up-regulated and 2479 down-regulated) were significantly differentially expressed in the O-T2DM group compared with the Control group. The biological function of DEmRNAs was subsequently investigated using WGCNA and enrichment assays. Pathway analysis revealed that the differentially expressed mRNAs were enriched in T cell receptor, cellular senescence, NK cell-mediated cytotoxicity, IL-17, lipids and atherosclerosis, actin cytoskeleton, etc. The circRNA-miRNA-mRNA regulatory network constructed by combining theoretical prediction and clinical experimental data revealed the potential regulatory effects of hsa_circ_0060614 and hsa-mir-4668- 3p on MT2A gene. Expression levels of these three genes were verified in plasma samples from the O-T2DM group and the Control group using qRT-PCR. Our results provide a wealth of transcriptome data for further studies of obesity type 2 diabetes. The ceRNA regulatory network we obtained may have guiding significance for the diagnosis and treatment of O-T2DM.