Abstract
Although it has been proved that the epigenetic modification of DNA and histones is involved in the pathogenesis of systemic lupus erythematosus (SLE), there is no study to explore whether the modification of N6-methyladenosine (m6A) in RNA is involved. In this study, the mRNA levels of m6A “writers” (METTL3, MTEEL14, and WTAP), “erasers” (FTO and ALKBH5), and “readers” (YTHDF2) in peripheral blood were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The results demonstrated that the mRNA levels of METTL3, WTAP, FTO, ALKBH5, and YTHDF2 in peripheral blood from SLE patients were significantly decreased. The levels of ALKBH5 mRNA in SLE patients were associated with anti-dsDNA, antinucleosome, rash, and ulceration. Multivariate logistic regression analysis showed that the level of ALKBH5 mRNA in peripheral blood is a risk factor of SLE (P < 0.001). Moreover, our results suggested that there was a positive correlation between m6A“writers” (METTL3 and WTAP), “erasers” (FTO and ALKBH5), and “readers” (YTHDF2) in SLE patients. This study suggests that the mRNA level of ALKBH5 in peripheral blood may be involved in the pathogenesis of SLE.
Highlights
The systemic lupus erythematosus (SLE) is a chronic and incurable autoimmune disease characterized by intermittent episodes of increased disease activity that require treatment with immunosuppressive agents [1, 2]
To identify the expression levels of methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14), Wilms tumor 1associating protein (WTAP), alkB homolog 5 (ALKBH5), Fat mass and obesityassociated protein (FTO), and YTHDF2 in patients with SLE, the mRNA levels of these genes in peripheral blood were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in SLE patients and HCs
Data showed that the mRNA levels of METTL3, WTAP, ALKBH5, and FTO in peripheral blood of SLE patients significantly decreased compared to HCs (Figure 1)
Summary
The systemic lupus erythematosus (SLE) is a chronic and incurable autoimmune disease characterized by intermittent episodes of increased disease activity that require treatment with immunosuppressive agents [1, 2]. Existing studies have demonstrated that the dysfunction of immune cells such as T cells, B cells, monocytes, neutrophils, and dendritic cells plays important roles in the pathogenesis of SLE [3,4,5,6]. Epigenetic modifications have been demonstrated to play an important role in the genesis and development of SLE [8, 9]. N6-methyladenosine (m6A) modification is the most prevalent and evolutionarily conserved modification which occurs in most types of RNAs and in most organisms [10]. This modification can be installed by adenosine methyltransferases, reversed by demethylases, and recognized by some RNA-binding proteins [11]. Some RNA-binding proteins such as YT521-B homology domains 2 (YTHDF2) which can recognize m6A modification, decode the methylation code, and transform them into diverse functional signals are called m6A “readers” [14]
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