Regulatory Role of LncRNA TUG1 in Hypertrophic Scar Development through miR-627 and IGFR1 Signaling

Hypertrophic scar (HS) is a sequela of abnormal dermal repair, marked by the excessive proliferation of fibroblasts and dermal fibrosis. While long-non-coding RNAs (LncRNAs) have emerged as crucial modulators in HS, the underlying mechanisms are yet to be fully elucidated. Our study employed DNA Microarrays to analyze differentially expressed LncRNAs in HS and identified significant upregulation of TUG1. Further analysis based on the TargetScan database revealed that TUG1 has binding sites for miR-627 and its target gene IGFR1. Quantitative Real-Time PCR (qRT-PCR) confirmed the upregulation of TUG1 and IGFR1, and downregulation of miR-627 in HS samples. Subsequent assays, including qRT-PCR, luciferase reporter gene, and Western Blot, were conducted to explore the interactions between TUG1, miR-627, and IGFR1. MTT and Transwell assays assessed the proliferative and migratory abilities of hypertrophic scar fibroblasts (HSFs). Furthermore, the rabbit ear scar model supported our findings. We discovered that upregulation of TUG1 or downregulation of miR-627 facilitated HSF proliferation and migration, elucidating a negative regulatory relationship between TUG1 and miR-627. Mechanically, TUG1 competitively binds to miR-627, thus freeing IGFR1 for upregulation. In conclusion, TUG1 knockout can inhibit HSF proliferation and migration by upregulating miR-627, which subsequently downregulates IGFR1. These findings offer novel insights for the effective treatment of HS.