miR-203a controls keratinocyte proliferation and differentiation via targeting the stemness-associated factor ΔNp63 and establishing a regulatory circuit with SNAI2

Abstract

Keratinocyte differentiation plays a pivotal role in the function of epidermal barrier and can be triggered by extracellular calcium in vitro and in vivo, but the precise mechanism still need to be further investigated. On the other hand, it is known that microRNAs control multiple biological events including cellular proliferation and differentiation. The present study demonstrated that miR-203a expression was upregulated in calcium-induced HaCaT Cells in a dose-dependent manner, whereas the stemness-associated factors SNAI2 and ΔNp63 were downregulated. Furthermore, SNAI2 and ΔNp63 were identified as the targets of miR-203a by computational prediction and luciferase reporter assays. The protein levels of SNAI2 and ΔNp63 were suppressed by ectopic expression of miR-203a. Functionally, silencing of miR-203a or overexpression of SNAI2 and ΔNp63 attenuated cell cycle arrest induced by calcium without any changes in cellular apoptosis. Additionally, ectopic expression of SNAI2 inhibited miR-203a in calcium-induced HaCaT cells, by binding to the promoter region of miR-203a. In conclusion, our findings demonstrate that miR-203a plays an essential role in keratinocyte proliferation and differentiation caused by extracellular calcium by targeting the SNAI2 and ΔNp63 genes. Furthermore, SNAI2 was found to suppress the transcription of miR-203a. Our data highlights a coherent cross-talk between two transcription factors (SNAI2 and ΔNp63) and miR-203a in keratinocyte differentiation and epidermal development.

Keywords: Epidermal differentiation; Keratinocyte; SNAI2; miR-203a; ΔNp63.