miR-4521 regulates keratinocyte function after burn injury by targeting GABARAPL2.

Abstract

Burn wound healing involves complex molecular events. This study sought to investigate the role of miR-4521 in burns by examining its expression in burned tissue and its regulation of keratinocyte function. Wound edge tissues from 116 burn patients and 102 normal skin samples were collected. miR-4521 expression was detected by qRT-PCR, followed by correlation analysis with clinical parameters and diagnostic evaluation. In vitro, cell viability was measured by CCK-8, inflammatory cytokines by ELISA, and oxidative stress markers by biochemical assays. The miR-4521 and GABARAPL2 interaction was validated through bioinformatic prediction combined with dual-luciferase and RIP assays. Expression of miR-4521 was markedly elevated in burn tissues compared to normal skin, with its levels positively correlating with burn surface area (r = 0.733), CRP (r = 0.661), and WBC count (r = 0.648). ROC curve analysis further suggested a diagnostic value for miR-4521 in burns, yielding an AUC of 0.849. In vitro, suppressing miR-4521 enhanced cell viability following heat injury while reducing inflammation, alongside alleviating oxidative stress. GABARAPL2, downregulated in burn tissues, was identified as a direct target of miR-4521 and inversely correlated with its expression (r = -0.704). In conclusion, The upregulation of miR-4521 in burn tissues showed close associations with both injury severity and inflammatory markers. By targeting GABARAPL2, miR-4521 inhibition attenuated heat-induced inflammation and oxidative stress in keratinocytes, positioning this microRNA as a possible therapeutic candidate for burn wound management.