LncRNA-ZNF252P-AS1/miR-15b-5p promotes the proliferation of keloid fibroblast by regulating the BTF3-STAT3 signaling pathway

JAK2/STAT3 signaling pathway plays an important role in keloid formation, but the upstream mechanism of their activation remains unclear. This study aims to investigate the possible mechanism of lncRNA-ZNF252P-AS1 in keloid. The differentially expressed genes in keloid and their upstream regulatory miRNAs and long non-coding RNAs (lncRNAs) were analyzed by bioinformatics database, and the targeting relationship was further verified by dual-luciferase reporter gene assay. LncRNA function as competitive endogenous RNA (ceRNA) in keloid was further verified by in keloid fibroblasts (KFs) and in nude mice with subcutaneous keloids. BTF3 expression was up-regulated in keloid tissues. The targeting relationship between BTF3 and miR-15b-5p was confirmed by dual-luciferase reporter gene assay. miR-15b-5p overexpression inhibited BTF3, Bcl-2, Cyclin D1, C-myc, Collagen I, MMP2, MMP9, N-cadherin, and ZEB2 expressions in KFs, inhibited cell proliferation and migration, while promoted E-cadherin levels. BTF3 overexpression reversed miR-15b-5p effects on KFs. Bioinformatics analysis as well as clinical and cellular experiments confirmed that the lncRNA ZNF252P-AS1 was highly expressed in keloid/KFs. Dual-luciferase reporter gene assays confirmed the targeting relationship between lncRNA ZNF252P-AS1 and miR-15b-5p. LncRNA ZNF252P-AS1 overexpression inhibited miR-15b-5p and E-cadherin levels, upregulated BTF3, Bcl-2, Cyclin D1, C-myc, Collagen I, MMP2, MMP9, N-cadherin, and ZEB2 expressions, increased cell proliferation and migration, and activated JAK2/STAT3 pathway, while miR-15b-5p overexpression reversed this effect. The in vivo results were consistent with in vitro results. In vivo experiments further confirmed that lncRNA ZNF252P-AS1 reduced keloid volume and weight. lncRNA ZNF252P-AS1 is a potential target for keloid treatment. •lncRNA ZNF252P-AS1 promoted ECM deposition and proliferation.•lncRNA-ZNF252P-AS1 participates in keloid formation.•lncRNA-ZNF252P-AS1 is a potential therapeutic target for keloid.