MiR‑122 and miR‑199 synergistically promote autophagy inoral lichen planus by targeting the Akt/mTOR pathway.

Abstract

The aim of the present study was to characterize the roles of two microRNAs (miRNAs), miR-122 and miR-199, in oral lichen planus (OLP). miRNA microarray analysis was performed to detect potential miRNAs involved in OLP, while in-silicon analysis, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot and immunohistochemistry (IHC) analyses were utilized to explore the molecular mechanisms underlying the roles of miR-199 and miR-122 in OLP. The results from the microarray and RT-qPCR analyses demonstrated that the expression levels of miR-122 and miR-199 were significantly decreased in the peripheral blood mononuclear cells (PBMCs) collected from the OLP group compared with the control group. In addition, miR-122 and miR-199 directly targeted AKT serine/threonine kinase 1 (AKT1) and mammalian target of rapamycin (mTOR), respectively, by binding to their 3′ UTRs. AKT1 and mTOR were highly expressed in PBMCs derived from OLP patients. In fact, a negative regulatory relationship was observed between miR-122 and AKT1, and between miR-199 and mTOR, with negative correlation coefficients of −0.41 and −0.51, respectively. Furthermore, the protein levels of AKT1, mTOR and microtubule associated protein 1 light chain 3β (LC3B) were upregulated in the OLP group compared with the control group. Finally, overexpression of miR-122 inhibited the expression of AKT1 and LC3B, while overexpression of miR-199 reduced the levels of mTOR and LC3B. In conclusion, the present study demonstrated that miR-199 and miR-122 are implicated in the pathogenesis of OLP by regulating the expression of mTOR and AKT1.