LncRNA KCNQ1OT1 promotes hypertrophic scar progression by regulating fibroblast proliferation, migration, and ECM accumulation via the miR-324-5p/SP1 axis.

OBJECTIVE: Hypertrophic scar (HTS) is a complex process involving abnormal fibroblast proliferation, migration, and extracellular matrix (ECM) accumulation. This study focused on long noncoding RNA KCNQ1OT1's expression and mechanism in HTS. METHODS: Differentially expressed lncRNAs (DELRNAs) were downloaded from the GEO database. RT-qPCR was conducted to assess the expression of KCNQ1OT1, miR-324-5p, SP1, and ECM components (α-SMA, COL1A1, and COL3A1). Pearson's correlation analysis was performed for KCNQ1OT1, miR-324-5p, and SP1 in HTS tissues. CCK-8, FCM, and Transwell assays assessed cell proliferation, apoptosis, cell cycle, and migration. DLR, RIP, and RNA pull-down assays confirmed the targeting of miR-324-5p to KCNQ1OT1 and SP1. RESULTS: KCNQ1OT1 was identified as a DElncRNA in dataset GSE181540. Both KCNQ1OT1 and SP1 were elevated in HTS tissues and fibroblast cell lines, whereas miR-324-5p was reduced. MiR-324-5p levels negatively correlated with KCNQ1OT1 and SP1 expression. Silencing KCNQ1OT1 inhibited HTS fibroblast proliferation, migration, and ECM component expression, and induced apoptosis and promoted G0/G1 phase arrest; these effects were reversed by the reduction of miR-324-5p. SP1 overexpression counteracted miR-324-5p's effects on cell proliferation, migration, and ECM accumulation. Mechanistically, KCNQ1OT1 acts as a miR-324-5p sponge, upregulating SP1 expression. CONCLUSION: Overall, KCNQ1OT1 promoted fibroblast proliferation, migration, and ECM accumulation by targeting the miR-324-5p/SP1 axis, inhibiting apoptosis, and accelerating HTS progression.