LINC01116 regulates proliferation, migration, and apoptosis of keloid fibroblasts by the TGF-β1/SMAD3 signaling via targeting miR-3141

Abstract

BackgroundKeloids 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. MethodsThe targeted relationship between microRNA (miR)-3141 and LINC01116 or transforming growth factor β1 (TGF-β1) was verified by dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays. The expression levels of LINC01116, miR-3141, TGF-β1, 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. ResultsOur 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-β1/SMAD3 signaling by directly targeting TGF-β1. Furthermore, TGF-β1 was identified as a direct and functional target of miR-3141. LINC01116 regulated the TGF-β1/SMAD3 signaling through miR-3141. Additionally, LINC01116 knockdown diminished the subcutaneous keloid growth in vivo. ConclusionOur findings demonstrated a novel mechanism, the miR-3141/TGF-β1/SMAD3 regulatory pathway, at least partially for the oncogenic role of LINC01116 in keloid formation.