Abstract
BACKGROUND: Th17 cell differentiation is involved in the development and progression of many diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Present study mainly focused on the role of LINC-XIST in Th17 cell differentiation. METHODS: The naïve CD4+ T cells were isolated from human whole blood. Cells were cultured under Th17 cell-polarizing condition for 6 days. The expression of LINC-XIST and miR-153-3p was measured by qPCR. The relationship between LINC-XIST, miR-153-3p, and ETS1 was predicted by TargetScan website and authenticated by luciferase reporter assay. ELISA assays were conducted to evaluate the IL-17 concentration. Western blot was utilized to measure the protein expression of ETS1. Th17 cell frequency was examined by flow cytometry. RESULTS: The expression of XIST markedly decreased and miR-153-3p expression markedly increased with Th17 cell differentiation. The mRNA expression of IL-17, IL-17 concentration, and Th17 cell frequency were observably decreased in overexpressed LINC-XIST group. Luciferase reporter assay authenticated that miR-153-5p was directly regulated by LINC-XIST. miR-153-3p inhibitor observably decreased IL-17 concentration, mRNA expression of IL-17, and Th17 cell frequency while si-XIST reversed this impact. ETS1 was confirmed to be regulated by miR-153-5p via luciferase reporter assay. In addition, ETS1 markedly decreased IL-17 mRNA expression, IL-17 concentration, and Th17 cell frequency while miR-153-5p mimic reversed this impact. CONCLUSION: LNCRNA XIST inhibited miR-377-3p to hinder Th17 cell differentiation through upregulating ETS1.