DNA methyltransferases-associated long non-coding RNA PRKCQ-AS1 regulate DNA methylation in myelodysplastic syndrome

IF 2.2 4区医学 Q3 HEMATOLOGY

International Journal of Laboratory Hematology Pub Date : 2024-04-28 DOI:10.1111/ijlh.14297

Jian Wen, Yongbin Wu, Quanfang Luo

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引用次数: 0

Abstract

Introduction

Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic stem cell disorders. DNA hypermethylation is considered to be the key mechanism of pathogenesis for MDS. Studies have demonstrated that DNA methylation can be regulated by the co-effect between long non-coding RNAs (lncRNAs) and DNA methyltransferases (DNMTs). The aim of this study was to identify DNMTs-associated differentially expressed (DE) lncRNAs, which may be a novel diagnostic and therapeutic target for MDS.

Methods

Two gene expression profile datasets (GSE4619 and GSE19429) were downloaded from the Gene Expression Omnibus (GEO) database. Systematic bioinformatics analysis was conducted. Then we verified the expression of PRKCQ-AS1 in MDS patients and features in SKM-1 cells.

Results

Bioinformatics analysis revealed that the DNMT-associated DE-lncRNA PRKCQ-AS1 was functionally related to DNA methylation. The target genes of PRKCQ-AS1 associated with DNA methylation are mainly methionine synthetase (MTR) and ten-eleven-translocation 1 (TET1). Moreover, the high expression of PRKCQ-AS1 was verified in real MDS cases. Further cellular analysis in SKM-1 cells revealed that overexpressed PRKCQ-AS1 promoted methylation levels of long interspersed nuclear element 1 (LINE-1) and cell proliferation, and apparently elevated both mRNA and protein levels of MTR and TET1, while knockdown of PRKCQ-AS1 showed opposite trend in SKM-1 cells.

Conclusion

DNMT-associated DE-lncRNA PRKCQ-AS1 may affects DNA methylation levels by regulating MTR and TET1.

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DNA 甲基转移酶相关长非编码 RNA PRKCQ-AS1 在骨髓增生异常综合征中调控 DNA 甲基化

导言骨髓增生异常综合征（MDS）是一组克隆性造血干细胞疾病。DNA甲基化过高被认为是MDS发病的关键机制。研究表明，DNA甲基化可受长非编码RNA（lncRNAs）和DNA甲基转移酶（DNMTs）的共同作用调控。本研究的目的是鉴定与DNMTs相关的差异表达（DE）lncRNAs，这些lncRNAs可能是MDS的新型诊断和治疗靶点。我们进行了系统的生物信息学分析。结果生物信息学分析表明，DNMT相关DE-lncRNA PRKCQ-AS1在功能上与DNA甲基化有关。PRKCQ-AS1与DNA甲基化相关的靶基因主要是蛋氨酸合成酶（MTR）和十七转位1（TET1）。此外，PRKCQ-AS1的高表达也在真实的MDS病例中得到了验证。在SKM-1细胞中的进一步细胞分析表明，过表达的PRKCQ-AS1促进了长间隔核元素1（LINE-1）的甲基化水平和细胞增殖，并明显升高了MTR和TET1的mRNA和蛋白水平，而敲除PRKCQ-AS1在SKM-1细胞中显示出相反的趋势。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Laboratory Hematology 医学-血液学

CiteScore

4.50

自引率

6.70%

发文量

211

审稿时长

6-12 weeks

期刊介绍： The International Journal of Laboratory Hematology provides a forum for the communication of new developments, research topics and the practice of laboratory haematology. The journal publishes invited reviews, full length original articles, and correspondence. The International Journal of Laboratory Hematology is the official journal of the International Society for Laboratory Hematology, which addresses the following sub-disciplines: cellular analysis, flow cytometry, haemostasis and thrombosis, molecular diagnostics, haematology informatics, haemoglobinopathies, point of care testing, standards and guidelines. The journal was launched in 2006 as the successor to Clinical and Laboratory Hematology, which was first published in 1979. An active and positive editorial policy ensures that work of a high scientific standard is reported, in order to bridge the gap between practical and academic aspects of laboratory haematology.