长链非编码RNA NR2F1-AS1可作为糖尿病周围神经病变的诊断生物标志物，并通过调控miR-150-5p促进疾病进展。

Abstract

NR2F1-AS1 is elevated in DPN and has high accuracy in the diagnosis of DPN; • High NR2F1-AS1 level is closely correlated with severe nerve damage and poor treatment response; • Silencing NR2F1-AS1 alleviates high-glucose-induced Schwann cell dysfunction and injury; • NR2F1-AS1 regulates the DPN pathological progression via NR2F1-AS1/miR-150-5p/TP53 axis. Background Diabetic peripheral neuropathy (DPN) is a common intractable complication of type 2 diabetes mellitus (T2DM), lacking specific diagnostic markers and therapeutic targets. Objectives This study explored the clinical value of NR2F1-AS1 in DPN and clarified its molecular regulatory mechanism in DPN progression, aiming to identify novel serum biomarkers and therapeutic targets for DPN. Methods This study enrolled 145 healthy volunteers, 182 T2DM patients, and 206 DPN patients. Serum NR2F1-AS1 expression was detected by qRT-PCR, and its diagnostic and predictive value was analyzed by ROC and logistic assays. RSC96 Schwann cell high-glucose model was constructed, and functional experiments (CCK-8, Transwell, and intracellular ATP content assay) and molecular experiments (qRT-PCR, WB, and ELISA) were used to verify the regulatory role of NR2F1-AS1 in DPN. The targeted regulatory relationship was verified by the dual-luciferase assays and RNA immunoprecipitation (RIP) assays. Results Serum NR2F1-AS1 was upregulated in DPN patients, with good diagnostic efficacy for DPN and predictive value for treatment response. Serum NR2F1-AS1 level was correlated with nerve conduction velocity and pain scores. Silencing NR2F1-AS1 alleviated high-glucose-induced Schwann cell injury. This protective effect was reflected in improved cell function and neurotrophic factor release, increased intracellular ATP content, and attenuation of mitochondrial dyshomeostasis, oxidative stress, and autophagy. NR2F1-AS1 directly targeted miR-150-5p which bound to TP53, and promoted DPN progression via the NR2F1-AS1/miR-150-5p/TP53 axis. Concl