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

  • Cell Death Dis. 2020 Jan 6;11(1):15. doi: 10.1038/s41419-019-2207-8.
Jie Du  1  2 ,  Ruifang Gao  3 ,  Yimei Wang  4 ,  Tivoli Nguyen  5 ,  Fang Yang  6 ,  Yongyan Shi  7 ,  Tianjing Liu  8 ,  Wang Liao  9 ,  Ran Li  3 ,  Fang Zhang  3 ,  Xuejun Ge  6 ,  Bin Zhao  10  11
Affiliations
  • 1. Department of Oral Medicine, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China. [email protected].
  • 2. Institute of Biomedical Research, Shanxi Medical University, Taiyuan, Shanxi, China. [email protected].
  • 3. Department of Oral Medicine, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China.
  • 4. Department of Endodontics, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China.
  • 5. Division of Biological Sciences, Department of Medicine, The University of Chicago, Chicago, IL, USA.
  • 6. Department of Periodontics, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China.
  • 7. Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
  • 8. Department of Pediatric Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
  • 9. Department of Cardiology, Hainan General Hospital, Hainan Clinical Medicine Research Institution, Haikou, China.
  • 10. Department of Oral Medicine, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China. [email protected].
  • 11. Department of prosthodontics, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China. [email protected].
PMID: 31907356 DOI: 10.1038/s41419-019-2207-8
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.

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