Department of Periodontics, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China.
Division of Biological Sciences, Department of Medicine, The University of Chicago, Chicago, Illinois, USA.
Sci Rep. 2020 Jan 15;10(1):301. doi: 10.1038/s41598-019-57288-9.
MicroRNA-27a/b are small non-coding RNAs which are reported to regulate inflammatory response and cell proliferation. Although some studies have demonstrated that miR-27b is down-regulated in the oral specimens of patients suffering with oral lichen planus (OLP), the molecular mechanism of miR-27b decrease remains a large mystery, and the expression of miR-27a in OLP is not well explored. Here, we demonstrated both miR-27a and miR-27b, compared with healthy controls, were reduced in the oral biopsies, serum and saliva samples derived from OLP patients. The reductions of miR-27a/b were also confirmed in the lipopolysaccharide (LPS)- or activated CD4 T cell-treated human oral keratinocytes (HOKs). Furthermore, we found vitamin D receptor (VDR) binding sites in the promoters of miR-27a/b genes and verified this finding. We also tested miR-27a/b levels in the oral epithelium from paricalcitol-treated, vitamin D deficient or VDR knockout mice. In the rescue experiments, we confirmed vitamin D and VDR inhibited LPS- or activated CD4 T cell-induced miR-27a/b reductions in HOKs. In sum, our results show that vitamin D/VDR signaling induces miR-27a/b in oral lichen planus.
miR-27a/b 是小的非编码 RNA,据报道可调节炎症反应和细胞增殖。尽管一些研究表明 miR-27b 在患有口腔扁平苔藓 (OLP) 的患者的口腔标本中下调,但 miR-27b 减少的分子机制仍不清楚,而且 miR-27a 在 OLP 中的表达也未得到充分探索。在这里,我们证明与健康对照组相比,miR-27a 和 miR-27b 在 OLP 患者的口腔活检、血清和唾液样本中减少。miR-27a/b 的减少也在脂多糖 (LPS) 或激活的 CD4 T 细胞处理的人口腔角质细胞 (HOK) 中得到证实。此外,我们在 miR-27a/b 基因的启动子中发现了维生素 D 受体 (VDR) 结合位点,并验证了这一发现。我们还在接受帕立骨化醇治疗、维生素 D 缺乏或 VDR 敲除的小鼠的口腔上皮中测试了 miR-27a/b 水平。在挽救实验中,我们证实维生素 D 和 VDR 抑制 LPS 或激活的 CD4 T 细胞诱导的 HOK 中 miR-27a/b 的减少。总之,我们的结果表明维生素 D/VDR 信号通路可诱导口腔扁平苔藓中的 miR-27a/b。