MicroRNA-26a/b have protective roles in oral lichen planus.

Abstract

Oral lichen planus (OLP) is a kind of oral epithelial disorder featured with keratinocyte apoptosis and inflammatory reaction. The pathogenesis of OLP remains an enigma. Herein, we showed that the levels of miR-26a/b were robustly down-regulated in oral mucosal biopsies, serum and saliva in OLP patients compared with healthy control. Moreover, we found the binding sites of vitamin D receptor (VDR) in the promoter regions of miR-26a/b genes and proved that the induction of miR-26a/b was VDR dependent. The reduction of miR-26a/b expression was also detected in the oral epithelium of vitamin D deficient or VDR knockout mice. miR-26a/b inhibitors enhanced apoptosis and Type 1T helper (Th1) cells-related cytokines production in oral keratinocytes, whereas miR-26a/b mimics were protective. Mechanistically, we analyzed miRNA target genes and confirmed that miR-26a/b blocked apoptosis by directly targeting Protein Kinase C δ (PKCδ) which promotes cellular apoptotic processes. Meanwhile, miR-26a/b suppressed Th1-related cytokines secretion through targeting cluster of the differentiation 38 (CD38). In accordant with miR-26a/b decreases, PKCδ and CD38 levels were highly elevated in OLP patients' samples. Taken together, our present investigations suggest that vitamin D/VDR-induced miR-26a/b take protective functions in OLP via both inhibiting apoptosis and impeding inflammatory response in oral keratinocytes.

• Authors: Jie Du, Ruifang Gao, Yimei Wang, Tivoli Nguyen, Fang Yang, Yongyan Shi, Tianjing Liu, Wang Liao, Ran Li, Fang Zhang, Xuejun Ge, Bin Zhao
• Journal: Cell death & disease (Cell Death Dis) Vol. 11 Issue 1 Pg. 15 (01 06 2020) ISSN: 2041-4889 [Electronic] England
• PMID: 31907356 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• MIRN26A microRNA, human
• MicroRNAs
• Receptors, Calcitriol
• Protein Kinase C-delta
• ADP-ribosyl Cyclase 1

Topics

• ADP-ribosyl Cyclase 1 (metabolism)
• Animals
• Apoptosis (genetics)
• Base Sequence
• Biopsy
• Cytokines (biosynthesis)
• Down-Regulation (genetics)
• Humans
• Keratinocytes (metabolism)
• Lichen Planus, Oral (genetics, immunology, pathology)
• Male
• Mice, Inbred C57BL
• Mice, Knockout
• MicroRNAs (genetics, metabolism)
• Models, Biological
• Mouth (pathology)
• Protein Kinase C-delta (metabolism)
• Receptors, Calcitriol (genetics)
• Response Elements (genetics)
• Th1 Cells (immunology)