A gene expression study suggests the possible involvement of IGF2BP2-related ncRNA network in Type 2 Diabetes

Aims: Genome-wide association studies (GWAS) have identified the IGF2BP2 (Insulin-like Growth Factor 2 mRNA binding protein 2) gene as a susceptibility locus for Type 2 diabetes mellitus (T2D). This study aimed to evaluate the IGF2BP2 mRNA levels in the blood of a cohort of T2D patients and to quantify the expression levels of non-coding RNAs (ncRNAs) that are predicted to interact with it. Methods: We extracted RNA from peripheral blood mononuclear cells of 50 T2D patients and 30 healthy controls (CTRL) and quantified, by qPCR, the IGF2BP2 expression levels. Using bioinformatics tools, we predicted its main ncRNAs target and quantified it. Results: The expression study showed a significantly higher IGF2BP2 level in T2D subjects than in CTRL. In silico analysis identified hsa-let7b-5p as a potential microRNA regulator of IGF2BP2, with reduced expression levels observed in T2D patients. Additionally, three lncRNAs (SNHG5, HOTAIR, and MEG3) were predicted as potential targets of IGF2BP2. Their expression levels were significantly elevated in T2D patients. In vitro assays demonstrated that inhibiting hsa-let7b-5p in HeLa cells resulted in increased expression of IGF2BP2 and the three lncRNAs. Conclusion: These findings highlight a potential regulatory network involving IGF2BP2, hsa-let7b-5p, and lncRNAs. This network may contribute to dysregulation of insulin/IGF signaling and glucose metabolism pathways, providing insights into T2D pathogenesis.