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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\u2013miR-627\u2013IGF1R axis plays a central role in HS pathogenesis and may serve as a promising therapeutic target for fibrotic skin disease.<\/jats:p>","DOI":"10.1007\/s10735-026-10814-2","type":"journal-article","created":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T01:52:59Z","timestamp":1780710779000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["LncRNA TUG1 promotes hypertrophic scar formation via the miR-627\/IGF1R axis"],"prefix":"10.1007","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1686-7514","authenticated-orcid":false,"given":"Zeming","family":"Bai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyang","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangzi","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rirui","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiwei","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GuYue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6335-4795","authenticated-orcid":false,"given":"Jiulong","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,6]]},"reference":[{"key":"10814_CR2","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1055\/s-0041-1731461","volume":"35","author":"N Barone","year":"2021","unstructured":"Barone N, Safran T, Vorstenbosch J, Davison PG, Cugno S, Murphy AM (2021) Current advances in hypertrophic scar and keloid management. 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The study was approved by the Medical Ethics Committee of the General Hospital of Northern Theater Command (Shenyang, China; R20210209). An informed consent document was signed by all patients before sample collection. The animal protocol of this study was reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) according to the guidelines of the Institutional Ethics Committee at Northern Theater General Hospital (Shenyang, China; R20210316). The study protocol was approved by the Ethics Committee of Northern Theater GeneralHospital ( R20190209).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}],"article-number":"186"}}