Hsa_circ_0006969 aggravates keratinocytes from high-glucose injury by sponging miR-375 to promote USP10 and SCD...

Diabetic foot ulcer (DFU) is a severe and frequent complication of diabetes, posing a major burden on patient well-being. Although circular RNAs (circRNAs) have been implicated in DFU pathogenesis, many disease-relevant circRNAs remain uncharacterized. Herein, we aimed to identify key circRNAs involved in DFU and elucidate their underlying molecular mechanisms. CircRNA expression profiles of DFU and non-DFU skin tissues were retrieved from the Gene Expression Omnibus (GEO) dataset GSE114248, and weighted gene co-expression network analysis (WGCNA) was applied to screen for DFU-associated hub circRNAs, which were then verified and confirmed by combining RT-qPCR in clinical samples. A high-glucose (HG) - treated human epidermal keratinocyte model was used to mimic the diabetic wound environment. The function of hsa_circ_0006969 was assessed by CCK-8, wound healing, and Western blot assays. Further bioinformatics prediction combined with dual-luciferase reporter, RIP-qPCR, and rescue experiments were performed to clarify molecular mechanism of hsa_circ_0006969. We found that hsa_circ_0006969 was significantly upregulated in skin tissues of DFU patients and HG - treated human epidermal keratinocyte model. The in vitro functional experiments proved that knockdown of hsa_circ_0006969 alleviated high glucose‑induced inhibition of keratinocyte proliferation and migration. Mechanistically, hsa_circ_0006969 acted as a molecular sponge for miR-375, thereby upregulating the expression of USP10 and SCD. Rescue experiments further demonstrated that the protective effect of hsa_circ_0006969 silencing against high‑glucose damage was reversed by miR-375 inhibition, confirming the involvement of the miR-375/USP10/SCD axis. Collectively, our study reveals that hsa_circ_0006969 promotes DFU progression through the miR-375/USP10/SCD axis and may represent a novel therapeutic target for DFU treatment.