LncRNA TUG1 promotes hypertrophic scar formation via the miR-627/IGF1R axis.

Hypertrophic scars (HS) are fibrotic skin disorders driven by abnormal fibroblast activity. The molecular mechanisms underlying HS remain incompletely understood, particularly the role of non-coding RNAs. Expression levels of lncRNA TUG1, miR-627, and IGF1R were measured in HS tissues and fibroblasts using qRT-PCR and Western blotting. Dual-luciferase assays validated direct interactions. Functional effects of TUG1 and miR-627 on fibroblast proliferation and migration were assessed using MTT and Transwell assays. A rabbit ear model of HS was used to examine in vivo effects of TUG1 and miR-627 modulation on scar formation and molecular expression. TUG1 was significantly upregulated in HS tissues and inversely correlated with miR-627, which was downregulated. TUG1 promoted fibroblast proliferation and migration by directly sponging miR-627, thereby lifting repression on IGF1R, a known pro-fibrotic effector. Luciferase assays confirmed direct binding of miR-627 to both TUG1 and IGF1R. Co-transfection of miR-627 attenuated TUG1-induced IGF1R upregulation and reversed its pro-fibrotic cellular effects. In vivo, TUG1 overexpression led to increased scar thickness, collagen deposition, and IGF1R expression, while miR-627 overexpression mitigated these effects. Co-administration of both restored scar morphology and molecular markers to near-control levels. TUG1 promotes hypertrophic scar formation by sponging miR-627 and derepressing IGF1R. This newly identified TUG1-miR-627-IGF1R axis plays a central role in HS pathogenesis and may serve as a promising therapeutic target for fibrotic skin disease.