Circ_PRKDC knockdown promotes skin wound healing by enhancing keratinocyte migration via miR-31/FBN1 axis.

Circular RNA protein kinase, DNA-activated, catalytic subunit (circ_PRKDC) has been found to impede wound healing in diabetic foot ulcers via regulating keratinocyte proliferation and migration. However, the mechanisms underlying circ_PRKDC in skin wound healing remain unclear. The expression of circ_PRKDC, microRNA (miR)-31 and fibrillin 1 (FBN1) was detected using quantitative reverse transcription-polymerase chain reaction and Western blot assays. The migration ability and the changes of matrix metallopeptidase 9 (MMP-9) and MMP2 levels were determined using wound healing, transwell and Western blot assays. The interaction between miR-31 and circ_PRKDC or FBN1 was verified by dual-luciferase reporter assay. The expression of circ_PRKDC was gradually down-regulated in wound edge at 1 and 7 days after injury relative to the unwounded skin. In human epidermal keratinocytes (HEKa), knockdown of circ_PRKDC promoted cell migration partly through up-regulating MMP-2 and MMP9, while circ_PRKDC overexpression showed opposite effects. In a mechanical study, we confirmed that miR-31 was a target of circ_PRKDC, and inhibition of miR-31 reversed the promotive effect of circ_PRKDC knockdown on HEKa migration. Besides that, miR-31 was verified to target FBN1, and ectopic overexpression of miR-31 accelerated HEKa migration via FBN1. Importantly, we also demonstrated that FBN1 overexpression attenuated the effects of circ_PRKDC knockdown on HEKa migration. In all, circ_PRKDC knockdown promoted HEKa migration during wound healing through miR-31/FBN1 axis, suggesting the therapeutic potential for circ_PRKDC on skin wound healing.
(© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)