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.