{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:34:33Z","timestamp":1791394473258,"version":"4.3.3"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T00:00:00Z","timestamp":1730937600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Diabetic foot ulcers (DFU) are one of the most destructive complications of diabetes mellitus. The aim of this study was to link miR\u2010155 and SOX2 with DFU to explore the regulation of wound healing by DFU and its potential mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human keratinocytes (HaCaT) were induced with advanced glycation end products (AGEs) to construct DFU models in vitro. AGE\u2010induced HaCaT\u00a0cells were subjected to CCK\u20108 assays, flow cytometry, and wound healing assays to evaluate cell proliferation, apoptosis, and migration capacity, respectively. RT\u2013qPCR and Western blotting were used to determine gene and protein expression levels, respectively. N6\u2010methyladenosine (M6A) levels in total RNA were assessed using an M6A methylation quantification kit.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results suggested that the inhibition of miR\u2010155 promoted wound healing in an in vitro DFU model, while the knockdown of HIF\u20101\u03b1 reversed this process, and that HIF\u20101\u03b1 was a target protein of miR\u2010155. In addition, knockdown of HIF\u20101\u03b1 promoted the m6A level of SOX2 mRNA, inhibited the expression of SOX2, and inhibited the activation of the EGFR\/MEK\/ERK signaling pathway, thus inhibiting the proliferation and migration of HaCaT\u00a0cells and promoting the apoptosis of HaCaT\u00a0cells, while overexpression of SOX2 reversed this effect. We also found that METTL3 knockdown had the opposite effect of HIF\u20101\u03b1 knockdown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Inhibition of miR\u2010155 promoted the expression of HIF\u20101\u03b1 and attenuated the m6A modification of SOX2 mRNA, thereby promoting the expression of SOX2 and activating the downstream EGFR\/MEK\/ERK signaling pathway to promote wound healing in an in vitro DFU model.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdi.14327","type":"journal-article","created":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T17:45:42Z","timestamp":1731001542000},"page":"60-71","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["<scp>miR<\/scp>\u2010155 promotes <scp>m6A<\/scp> modification of <scp>SOX2 mRNA<\/scp> through targeted regulation of <scp>HIF<\/scp>\u20101\u03b1 and delays wound healing in diabetic foot ulcer in vitro 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