MicroRNA-122 promotes apoptosis of keratinocytes in oral lichen planus through suppressing VDR expression

Abstract

MicroRNA-122 (miR-122) is known to be up-regulated by inflammation to exert a variety of biological functions in hepatocellular carcinoma (HCC)-derived human cell lines. Vitamin D receptor (VDR) is reported to regulate excessive oral keratinocytes apoptosis which compromises oral epithelial barrier in oral lichen planus (OLP). Although many studies have suggested that miR-122 is capable of regulating cell apoptosis, its effects on the development of OLP and VDR expression are still unclear. Herein, we demonstrate that miR-122 expression is increased in the epithelial layer of OLP. Mechanically, transcription factor nuclear factor-κB (NF-κB) selectively binds with κB element in the promoter of miR-122 to accelerate gene transcription. The up-regulation of miR-122 induces cell apoptosis in human oral keratinocytes (HOKs) by targeting VDR mRNA. In VDR knockout oral keratinocytes, miR-122 fails to improve caspase 3 activity and cleaved caspase 3 and poly(ADP-ribose) polymerase (PARP) levels. Moreover, VDR overexpression is able to reverse lipopolysaccharide (LPS)- or activated CD4+ T cell-induced miR-122 up-regulation and ameliorate miR-122-stimulated caspase 3 activity. Collectively, our results suggest that miR-122 promotes oral keratinocytes apoptosis in OLP through decreasing VDR expression.

Keywords: apoptosis; miR-122; oral lichen planus; vitamin D receptor.