Clinical significance of miR-506-5p in type 2 diabetes mellitus and its regulatory effect on pancreatic β-cell proliferation

INTRODUCTION: One of the core pathological features of type 2 diabetes mellitus (T2DM) is pancreatic β-cell dysfunction. MicroRNAs, askey regulatory molecules, have emerged as pivotal post-transcriptional regulators of β-cell homeostasis, but their specific regulatorymechanisms require further clarification. This study aimed to investigate the expression characteristics and diagnostic value of miR-506-5pin T2DM and its regulatory mechanism in pancreatic β-cell function. MATERIAL AND METHODS: A total of 45 healthy controls and 48 patients with T2DM were enrolled. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to quantify peripheral blood miR-506-5p and p21-activated kinase 1 (PAK1) levels, and theircorrelations with clinical indicators and diagnostic efficacy were analyzed. Using INS-1 cells as the model, overexpression or knockdown ofmiR-506-5p was achieved by transfecting miR-506-5p mimic/inhibitor. Combined with a dual-luciferase reporter gene assay and functionalrescue experiment, the target molecule and regulatory role of miR-506-5p were clarified. RESULTS: miR-506-5p expression was significantly elevated in patients with T2DM, whereas PAK1 expression was significantly decreased. The area under the curve (AUC) of miR-506-5p for diagnosing T2DM was 0.904, and it was positively correlated with fasting plasmaglucose (FPG) and glycated hemoglobin (HbA1c). Cell experiment results showed that high glucose could upregulate miR-506-5p expression. Overexpression of miR-506-5p suppressed pancreatic β-cell viability, promoted apoptosis, and reduced insulin secretion, whereas knockdown reversed these effects. miR-506-5p could directly target PAK1 and negatively regulate its expression, and knockdown of PAK1 could reverse the protective effect of miR-506-5p inhibitor. CONCLUSIONS: miR-506-5p is highly expressed in T2DM, regulates pancreatic β-cell function by targeting and inhibiting PAK1, and participatesin the pathogenesis of T2DM.