Downregulation of microRNA-101-3p participates in systemic lupus erythematosus progression via negatively regulating HDAC9.

Abstract

This study aimed to investigate the mechanism of microRNA-101-3p (miR-101-3p) on the progression of systemic lupus erythematosus (SLE). The human peripheral blood mononuclear cells (PBMCs) were isolated from whole blood samples of SLE patients and healthy individuals, followed by cell culture and transfection. Moreover, the flow cytometry assay, quantitative real-time reverse-transcription polymerase chain reaction, Western blot, and enzyme-linked immunoassay were used to assess the effect of miR-101-3p on PBMCs. Bioinformatics analysis was conducted to predict the putative target gene of miR-101-3p, luciferase reporter gene assay, and RNA pull-down assay were applied to verify the interaction between them. Compared with healthy individuals, the expression level of miR-101-3p in PBMCs of SLE patients was significantly decreased, whereas interleukin (IL)-17A, IL-6, and interferon (IFN)-γ were remarkably increased (all P < .001). Correlation analyses showed that there were negative correlations between miR-101-3p and IL-17A, IL-6 and IFN-γ. The expression level of miR-101-3p in PBMCs of SLE patients was positively correlated with C3 expression (rs = .4075; P = .0229), while negatively associated with erythrocyte sedimentation rate (ESR) (rs = -.4238; P = .0175) and IgG expression (rs = -.4949; P = .0047). Overexpression of miR-101-3p could inhibit the differentiation of CD4 + T cells into Th17 lineage. Histone deacetylase 9 (HDAC9) was identified as a potential target gene of miR-101-3p. Furthermore, HDAC9 abolished the effect of miR-101-3p on Th17 cell differentiation and IL-17A expression in SLE. In conclusion, downregulated miR-101-3p in PBMCs of SLE patients inhibited Th17 cell differentiation by directly targeting HDAC9, which could be used as a novel therapeutic therapy for SLE treatment.