miR-542-3p targets ATG7 to regulate viability and profibrotic marker expression in human keloid fibroblasts

Keloids are characterized by persistent fibroblast activation and excessive extracellular matrix (ECM) accumulation. This study aimed to clarify the role of miR-542-3p in keloid fibroblasts and to determine whether ATG7 functions as a direct downstream mediator regulating fibroblast viability/apoptosis and profibrotic protein expression. Human keloid fibroblasts (HKFs) and human skin fibroblasts (HSFs) were used. miR-542-3p expression was quantified by RT-qPCR. HKFs were transfected with miR-542-3p mimic/inhibitor and corresponding negative controls. Cell viability was assessed using CCK-8, and apoptosis was evaluated by Annexin V-FITC/PI flow cytometry. Protein levels of collagen I, collagen III and α-SMA were examined by western blotting. Direct targeting of ATG7 by miR-542-3p was tested using wild-type/mutant ATG7 3'-UTR dual-luciferase reporter assays. ATG7 knockdown (si-ATG7) and epistasis (miR-542-3p inhibitor ± si-ATG7) experiments were performed to assess functional dependency. miR-542-3p was significantly upregulated in HKFs compared with HSFs. miR-542-3p inhibition reduced HKF viability and increased apoptosis, whereas miR-542-3p overexpression showed the opposite trend. miR-542-3p positively regulated collagen I, collagen III and α-SMA protein levels. Dual-luciferase assays confirmed that miR-542-3p directly binds the ATG7 3'-UTR, and ATG7 protein abundance was inversely regulated by miR-542-3p. Functionally, ATG7 knockdown increased HKF viability and elevated profibrotic marker expression, and it attenuated the anti-fibrotic effects induced by miR-542-3p inhibition. miR-542-3p promotes a pro-survival, profibrotic phenotype in keloid fibroblasts by directly targeting ATG7. The miR-542-3p/ATG7 axis may represent a mechanistically supported candidate pathway for further investigation in keloid fibrosis.