Circ_0084443 Inhibits Wound Healing Via Repressing Keratinocyte Migration Through Targeting the miR-17-3p/FOXO4 Axis.

ABSTRACT

Keratinocyte migration is a crucial process during skin wound healing, and circular RNAs are associated with keratinocyte migration. The purpose of our study was to clarify the role of circ_0084443 in wound healing. The levels of circ_0084443, microRNA (miR)-17-3p, and forkhead box protein O4 (FOXO4) were examined by quantitative reverse transcription-PCR. Cell migration was detected via wound scratch assay or transwell assay. The protein expression was measured using western blot. The binding analysis between miR-17-3p and circ_0084443 or FOXO4 was determined by dual-luciferase reporter assay and RNA Immunoprecipitation assay. TGF-ß1 decreased the levels of circ_0084443 and FOXO4 while increased the miR-17-3p expression in keratinocytes by a concentration-dependent manner. Circ_0084443 acted as a miR-17-3p sponge and circ_0084443 overexpression alleviated TGF-ß1-induced migration of keratinocytes by sponging miR-17-3p. FOXO4 was a target for miR-17-3p. The downregulation of miR-17-3p suppressed cell migration in TGF-ß1-induced cells by increasing the FOXO4 level. Circ_0084443 positively regulated the FOXO4 expression by sponging miR-17-3p. Circ_0084443 suppressed the TGFß signaling pathway by affecting the miR-17-3p/FOXO4 axis. These results exhibited that circ_0084443 suppressed the TGF-ß1-induced keratinocyte migration by regulating the miR-17-3p/FOXO4 axis, suggesting the application potential of circ_0084443 in wound-healing-related diseases.