miR‑101‑3p negatively regulates inflammation in systemic lupus erythematosus via MAPK1 targeting and inhibition of the NF‑κB pathway

Abstract

Systemic lupus erythematosus (SLE) is an autoim‑ mune disease often used as a model in genomics research. The downregulation of microRNA‑101‑3p (miR‑101‑3p) participates in the progression of SLE, although the under‑ lying mechanisms remain to be elucidated. The present study aimed to evaluate the specific roles of miR‑101‑3p in the SLE inflammatory response and its potential mechanisms. Reverse transcription‑quantitative (RT‑q) PCR was used to profile miR‑101‑3p expression in the peripheral blood mononuclear cells (PBMCs) from 40 female patients with SLE and 20 female healthy volunteers. The interactions between miR‑101‑3p and MAPK1 were identified and evaluated using dual‑luciferase reporter and RNA pull‑down assays. The levels of IL‑10 and IFN‑γ were evaluated by enzyme‑linked immunosorbent assay. The expression of NF‑κB p65 and phosphorylated IκBα were evaluated using western blotting. miR‑101‑3p expres‑ sion was demonstrated to be downregulated in SLE PBMCs. miR‑101‑3p negatively regulated IL‑10 and IFN‑γ expression in SLE samples and was demonstrated to target MAPK1. Increases in MAPK1 expression eliminated miR‑101‑3p inhibition of IL‑10 and IFN‑γ. MAPK1 activated the NF‑κB pathway in SLE PBMCs and this activation was inhibited when miR‑101‑3p was overexpressed. In addition, treatment with BAY11‑7085 (NF‑κB activator) was demonstrated to reverse the inhibitory effects of miR‑101‑3p expression on both IL‑10 and IFN‑γ in SLE PBMCs. BAY11‑7082 also markedly reduced MAPK1‑induced increases in IL‑10 and IFN‑γ in SLE PBMCs. miR‑101‑3p overexpression attenu‑ ated the inflammatory response in SLE PBMCs by inhibiting the expression of MAPK1 and blocking the NF‑κB pathway. The results revealed a novel regulatory mechanism in SLE inflammation and offer a new direction for the development of SLE treatments.