Diabetology & Metabolic Syndrome · 10 authors, 2 centres
This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.
This study found that lncRNA XIST and EGFR are downregulated while miR-126-3p is upregulated in diabetic foot ulcer tissues and high-glucose-treated keratinocytes. Silencing XIST further inhibited cell proliferation and migration by upregulating miR-126-3p and downregulating EGFR, suggesting that the XIST/miR-126-3p/EGFR axis is a potential therapeutic target for diabetic foot ulcers.
**Background:** Diabetic foot ulcers (DFUs) are a severe complication of diabetes, with high prevalence, recurrence, and mortality. Long noncoding RNA XIST (lncRNA XIST) has been implicated in various diseases but its role in DFUs is unclear. This study investigates the involvement of lncRNA XIST, miR-126-3p, and EGFR in DFU pathogenesis.
**Methods:** A diabetic ulcer rat model was established using a high-sugar/high-fat diet and streptozotocin (STZ) injection, followed by a full-thickness skin wound and glacial acetic acid application. Skin tissues were analyzed by HE, Masson, and IHC staining. HaCaT cells were cultured in high glucose (22.5 g/L) to simulate hyperglycemia. Gene expression was measured by RT-qPCR and Western blot. Cell proliferation was assessed by CCK-8 assay, and migration by Transwell and wound healing assays. Luciferase reporter assays confirmed binding between XIST and miR-126-3p, and between miR-126-3p and EGFR. Lentiviral vectors were used for XIST silencing (sh-XIST) and EGFR overexpression (oe-EGFR); a miR-126-3p inhibitor was also used.
**Key Results:** In diabetic ulcer rat skin, XIST and EGFR were downregulated, while miR-126-3p was upregulated compared to normal skin (P < 0.05). High glucose reduced HaCaT cell viability and migration. Silencing XIST further decreased cell proliferation and migration under high glucose (P < 0.01). Luciferase assays confirmed that XIST binds miR-126-3p, and miR-126-3p targets EGFR. Silencing XIST increased miR-126-3p and decreased EGFR expression. A miR-126-3p inhibitor reversed the effects of XIST silencing, enhancing proliferation and migration. EGFR overexpression also promoted cell proliferation and migration under high glucose.
**Clinical Implications:** This study identifies the lncRNA XIST/miR-126-3p/EGFR axis as a key regulator of keratinocyte function in DFUs. Downregulation of XIST under hyperglycemia leads to increased miR-126-3p, which suppresses EGFR, impairing wound healing. Targeting this axis may offer new therapeutic strategies for DFUs, such as restoring XIST or inhibiting miR-126-3p to enhance EGFR-mediated keratinocyte proliferation and migration.