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Published on: November 1, 2015
The study of METTL14, ALKBH5, and YTHDF2 in peripheral blood mononuclear cells from systemic lupus erythematosus
Qing Luo1, Jiayue Rao1, Lu Zhang1
1Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Background:
This study was aimed to explore the mRNA expression of m6A "writers" (METTL3, MTEEL14, and WTAP), "erasers" (FTO and ALKBH5), and "readers" (YTHDF2) in peripheral blood mononuclear cells (PBMCs) from systemic lupus erythematosus (SLE) patients and investigate the relation between their expressions with clinical features.
Methods:
In all, 54 SLE patients and 42 healthy controls (HC) were included in the current study. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to investigate the mRNA expression of m6A "writers," "erasers," and "readers" in PBMCs from SLE patients and HC.
Results:
Decreased mRNA expression of MTEEL14, ALKBH5, and YTHDF2 was observed in SLE patients compared with those in HC (p < .001). The decreased mRNA expression of METTL14 was associated with white blood cell count (WBC) and monocyte count (M), this decreased mRNA expression of ALKBH5 was associated with C-reactive protein (CRP), neutrophil percentage (N%), lymphocyte percentage (L%), neutrophil-lymphocyte ratio (NLR), complement 3 (C3), and fever, and the decreased mRNA expression of YTHDF2 was associated with L%, NLR, C3, and fever. In addition, there was a positive correlation between mRNA expression of METTL14, ALKBH5, and YTHDF2 in PBMCs from SLE patients. Importantly, logistic regression analysis revealed that decreased mRNA expression of YTHDF2 was a risk factor for SLE.
Conclusion:
Taken all together, our findings suggested decreased YTHDF2 that was associated with disease activity may play an important role in the pathogenesis of SLE, METTL14 and ALKBH5 may be concomitantly decreased.
Insights
This study found decreased YTHDF2 mRNA in systemic lupus erythematosus (SLE) patients, suggesting it plays a role in SLE pathogenesis and is a risk factor. METTL14 and ALKBH5 were also decreased.
Area of Science:
- Immunology
- Molecular Biology
- Epigenetics
Background:
- Systemic lupus erythematosus (SLE) is a chronic autoimmune disease.
- The role of RNA methylation, specifically N6-methyladenosine (m6A), in SLE pathogenesis is not fully understood.
- m6A modification involves "writers", "erasers", and "readers" that regulate gene expression.
Purpose of the Study:
- To investigate the mRNA expression levels of key m6A regulators (writers, erasers, readers) in peripheral blood mononuclear cells (PBMCs) of SLE patients.
- To explore the correlation between the expression of these m6A regulators and clinical features of SLE.
- To determine if m6A regulators are potential risk factors for SLE.
Main Methods:
- Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was employed.
- PBMCs were collected from 54 SLE patients and 42 healthy controls (HC).
- mRNA expression of METTL3, METTL14, WTAP (writers), FTO, ALKBH5 (erasers), and YTHDF2 (reader) was analyzed.
Main Results:
- Significantly decreased mRNA expression of METTL14, ALKBH5, and YTHDF2 was observed in SLE patients compared to HC.
- Decreased METTL14 expression correlated with white blood cell and monocyte counts.
- Decreased ALKBH5 and YTHDF2 expression correlated with various clinical parameters including C-reactive protein, lymphocyte percentage, neutrophil-lymphocyte ratio, and fever. Logistic regression identified decreased YTHDF2 as a risk factor for SLE.
Conclusions:
- Reduced YTHDF2 mRNA expression is associated with SLE disease activity and may be a significant factor in SLE pathogenesis.
- METTL14 and ALKBH5 mRNA expression are also decreased in SLE patients, potentially playing a concurrent role.
- YTHDF2 warrants further investigation as a potential therapeutic target or biomarker for SLE.
