LncRNA NR2F1-AS1 serves as a diagnostic biomarker for diabetic peripheral neuropathy and promotes disease progression by regulating miR-150-5p.

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. CONCLUSION: NR2F1-AS1 serves as a potential non-invasive biomarker and promising therapeutic target for DPN by driving Schwann cell dysfunction via the NR2F1-AS1/miR-150-5p/TP53 axis.