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Abstract Keloids are pathological scar tissue resulting from skin trauma or spontaneous formation, often accompanied by itching and pain. Although GNAS antisense RNA 1 (GNAS‐AS1) shows abnormal upregulation in keloids, the underlying molecular mechanism is unclear. The levels of genes and proteins in clinical tissues from patients with keloids and human keloid fibroblasts (HKFs) were measured using quantitative reverse transcription PCR, western blot and enzyme‐linked immunosorbent assay. The features of HKFs, including proliferation and migration, were evaluated using cell counting kit 8 and a wound healing assay. The colocalization of GNAS‐AS1 and miR‐196a‐5p in HKFs was measured using fluorescence in situ hybridization. The relationships among GNAS‐AS1, miR‐196a‐5p and C‐X‐C motif chemokine ligand 12 (CXCL12) in samples from patients with keloids were analysed by Pearson correlation analysis. Gene interactions were validated by chromatin immunoprecipitation and luciferase reporter assays. GNAS‐AS1 and CXCL12 expression were upregulated and miR‐196a‐5p expression was downregulated in clinical tissues from patients with keloids. GNAS‐AS1 knockdown inhibited proliferation, migration, and extracellular matrix (ECM) accumulation of HKFs, all of which were reversed by miR‐196a‐5p downregulation. Signal transducer and activator of transcription 3 (STAT3) induced GNAS‐AS1 transcription through GNAS‐AS1 promoter interaction, and niclosamide, a STAT3 inhibitor, decreased GNAS‐AS1 expression. GNAS‐AS1 positively regulated CXCL12 by sponging miR‐196‐5p. Furthermore, CXCL12 knockdown restrained STAT3 phosphorylation in HKFs. Our findings revealed a feedback loop of STAT3/GNAS‐AS1/miR‐196a‐5p/CXCL12/STAT3 that promoted HKF proliferation, migration and ECM accumulation and affected keloid progression.
Liu et al. (Sat,) studied this question.