Involvement of N6-methyladenosine modifications of long noncoding RNAs in systemic lupus erythematosus.

ABSTRACT

BACKGROUND: LncRNAs are potential biomarkers for SLE, but the epigenetic regulatory mechanisms of N6-methyladenosine (m6A) modification in SLE remain largely unclear. METHODS: In this study, we established m6A modification profile and investigated the potential roles of m6A-related lncRNAs in SLE. The m6A modification profile of SLE was established using MeRIP-seq. Four potential m6A related-lncRNAs (linc02446, linc01410, Xist, and PSMB8-AS1) were selected for validation using qRT-PCR, and their expression and association with clinical characteristics with SLE were evaluated. RESULTS: Overall, m6A level was lower in patients with SLE than in controls. Compared with controls, the expression of the two m6A related-lncRNAs (Xist and PSMB8-AS1) was downregulated in patients with SLE (all P < 0.05); the linc02446 was up-regulated in PBMCs of patients with SLE (Z=-2.738, P = 0.006), while it was not differentially expressed in T cells (Z=-0.387, P = 0.699). No significant alteration in linc01410 expression was observed in patients (Z=-0.940, P = 0.347). The lower expression levels of Xist and PSMB8-AS1 were associated with many clinical manifestations in patients with SLE (all P < 0.05). Additionally, mRNAs co-expressed with m6A related-lncRNAs (Xist, linc02446, and PSMB8-AS1) also participated in SLE. CONCLUSION: These results suggest that m6A methylation and m6A related-lncRNAs might be involved in the pathogenesis of SLE. Thus, our findings provide some clues on the potential function of lncRNAs that m6A modification may target in novel therapeutic or diagnostic strategies for SLE.