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系统性红斑狼疮患者外周血单个核细胞中METTL14、ALKBH5和YTHDF2的研究

The study of METTL14, ALKBH5, and YTHDF2 in peripheral blood mononuclear cells from systemic lupus erythematosus.

作者信息

Luo Qing, Rao Jiayue, Zhang Lu, Fu Biqi, Guo Yang, Huang Zikun, Li Junming

机构信息

Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

Department of rheumatology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

出版信息

Mol Genet Genomic Med. 2020 Sep;8(9):e1298. doi: 10.1002/mgg3.1298. Epub 2020 Jun 25.

Abstract

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.

摘要

背景

本研究旨在探讨系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMC)中m6A“书写蛋白”(METTL3、METTL14和WTAP)、“擦除蛋白”(FTO和ALKBH5)和“阅读蛋白”(YTHDF2)的mRNA表达情况,并研究它们的表达与临床特征之间的关系。

方法

本研究共纳入54例SLE患者和42例健康对照(HC)。采用定量逆转录-聚合酶链反应(qRT-PCR)检测SLE患者和HC的PBMC中m6A“书写蛋白”、“擦除蛋白”和“阅读蛋白”的mRNA表达。

结果

与HC相比,SLE患者中METTL14、ALKBH5和YTHDF2的mRNA表达降低(p <.001)。METTL14的mRNA表达降低与白细胞计数(WBC)和单核细胞计数(M)相关,ALKBH5的mRNA表达降低与C反应蛋白(CRP)、中性粒细胞百分比(N%)、淋巴细胞百分比(L%)、中性粒细胞与淋巴细胞比值(NLR)、补体3(C3)和发热相关,YTHDF2的mRNA表达降低与L%、NLR、C3和发热相关。此外,SLE患者PBMC中METTL14、ALKBH5和YTHDF2的mRNA表达之间存在正相关。重要的是,逻辑回归分析显示YTHDF2的mRNA表达降低是SLE的一个危险因素。

结论

综上所述,我们的研究结果表明,与疾病活动相关的YTHDF2降低可能在SLE的发病机制中起重要作用,METTL14和ALKBH5可能同时降低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e52a/7507441/33dcda617411/MGG3-8-e1298-g001.jpg

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