Objectives: Systemic lupus erythematosus (SLE) is a typical autoimmune disease, which is associated with many factors, such as miRNAs. The effect of miRNAs encoded by X chromosome (X-linked miRNAs) plays a crucial role in autoimmune disease. This study aims to identify X-linked miRNAs and validate the pathway influenced by miRNAs in SLE.
Methods: Differentially expressed miRNAs (DEMs) encoded by X chromosome from PBMCs of SLE patients compared to healthy controls (HCs) and differentially expressed genes (DEGs) acquired from GSE50772 were analysed. The function and pathway enrichment analysis of the overlapping genes of target genes of X-linked miRNA and DEGs were performed, followed by investigating the hub genes. The expression of the identified miRNA (miR-548m) was verified in SLE patients. The relationship between miR-548m and PTEN was detected by increasing/decreasing miR-548m expression. The target of miR-548m on PTEN was confirmed by luciferase reporter assays.
Results: 104 DEMs (9 X-linked miRNAs) and 3071 DEGs were identified. The target genes of X-linked miRNAs and DEGs were intersected to obtain 114 consensus genes. Then the top 5 hub genes (FOS, PTEN, STAT1, GRB2, ITGA6) were screened and PTEN expression might have negative correlation with X-linked miR-548m in SLE patients. Upregulation of miR-548m significantly inhibited PTEN expression, while knocking down miR-548m increased PTEN expression. There was a miR-548m target in the nt219-nt225 region of PTEN 3́UTR.
Conclusions: X-linked miR-548m might target PTEN and play a role in SLE, which revealed a new molecular mechanism of X-linked miRNA in the development of SLE.