LINC01116 regulates proliferation, migration, and apoptosis of keloid fibroblasts by the TGF-131/SMAD3 signaling via targeting miR-3141

Background: Keloids are benign fibroproliferative skin tumors. Long non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of keloid formation. In this paper, we explored the precise actions of LINC01116 in keloid formation. Methods: The targeted relationship between microRNA (miR)-3141 and LINC01116 or transforming growth factor 131 (TGF-131) was verified by dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays. The expression levels of LINC01116, miR-3141, TGF-131, and SMAD family member 3 (SMAD3) were gauged by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Cell proliferation, migration, and apoptosis were assessed by the Cell Counting Kit-8 (CCK-8) assay, wound-healing assay, and flow cytometry, respectively. Animal studies were used to assess the role of LINC01116 in the subcutaneous keloid growth in vivo. Results: Our data showed that LINC01116 targeted miR-3141 by directly binding to miR-3141. LINC01116 was up-regulated and miR-3141 was down-regulated in human keloid tissues and fibroblasts. LINC01116 knockdown or miR-3141 overexpression suppressed keloid fibroblast proliferation, migration, and promoted cell apoptosis. Moreover, miR-3141 was a downstream mediator of LINC01116 function. MiR-3141 regulated the TGF-131/ SMAD3 signaling by directly targeting TGF-131. Furthermore, TGF-131 was identified as a direct and functional target of miR-3141. LINC01116 regulated the TGF-131/SMAD3 signaling through miR-3141. Additionally, LINC01116 knockdown diminished the subcutaneous keloid growth in vivo. Conclusion: Our findings demonstrated a novel mechanism, the miR-3141/TGF-131/SMAD3 regulatory pathway, at least partially for the oncogenic role of LINC01116 in keloid formation.