MicroRNA-194 Regulates Keratinocyte Proliferation And Differentiation By Targeting Grainyhead-like 2 In Psoriasis

Objectives:MicroRNAs(miRNAs)are currently emerged as important regulators in psoriasis.Psoriasis is characterized by hyperproliferation and impaired differentiation of keratinocytes in skin lesions.miR-194 is a well-known regulator of cell proliferation and differentiation.However,the role of miR-194 in psoriasis pathogenesis remains unclear.In this study we aimed to investigate the role of miR-194 in keratinocyte hyperproliferation and differentiation.Methods:15 cases of psoriasis in our hospital were selected,while 10 healthy subjects were selected as control.The expression of miR-194 and GRHL2 in biopsy skin was detected by RT-PCR and Western blot.MTT and BrdU were used to detect the proliferation of keratinocytes.In addition,miR-194 mimetic,miR-194 inhibitor and miR-194 control sequence were used to infect 293T cells to further confirm the effect of miR-194 on proliferation.The expression of CK-1 and CK-10 was detected by RT-PCR to investigate the effect of miR-194 on the differentiation of keratinocyte.The relationship between miR-194 and GRHL2 expression in psoriasis skin was observed by Spearman correlation analysis.Results:We found that miR-194 was significantly downregulated in psoriasis lesional skin.Overexpression of miR-194 inhibited the proliferation and promoted the differentiation of primary human keratinocytes,whereas miR-194 suppression promoted the proliferation and inhibited their differentiation.Bioinformatic analysis predicted that the Grainyhead-like 2(GRHL2)was a target gene of miR-194,which we further validated with a dual-luciferase reporter assay,real-time quantitative polymerase chain reaction(RT-qPCR),and Western blot analysis.The effect of miR-194 on cell proliferation and differentiation was significantly reversed by overexpression of GRHL2.Moreover,the expression of miR-194 and GRHL2 was inversely correlated in psoriasis lesional skin.Conclusions:Taken together,our results suggest that miR-194 inhibits the proliferation and promotes the differentiation of keratinocytes through targeting GRHL2.The downregulation of miR-194 expression may contribute to the pathogenesis of psoriasis and targeting miR-194 may represent a novel and potential therapeutic strategy for psoriasis.