DNA 甲基转移酶相关的长非编码 RNA PRKCQ-AS1 调节骨髓增生异常综合征中的 DNA 甲基化。

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

机构信息

Department of Hematology, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, Guangxi Zhuang Autonomous Region, China.

Department of Laboratory Medicine, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, Guangxi Zhuang Autonomous Region, China.

出版信息

Int J Lab Hematol. 2024 Oct;46(5):878-884. doi: 10.1111/ijlh.14297. Epub 2024 Apr 28.

DOI:10.1111/ijlh.14297

PMID:38679027

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.

摘要

简介

骨髓增生异常综合征（MDS）是一组克隆性造血干细胞疾病。DNA 超甲基化被认为是 MDS 发病机制的关键机制。研究表明，DNA 甲基化可以通过长非编码 RNA（lncRNA）和 DNA 甲基转移酶（DNMTs）的共同作用来调节。本研究旨在鉴定与 DNMT 相关的差异表达（DE）lncRNA，它们可能是 MDS 的一种新的诊断和治疗靶点。

方法

从基因表达综合数据库（GEO）下载了两个基因表达谱数据集（GSE4619 和 GSE19429）。进行了系统的生物信息学分析。然后，我们验证了 MDS 患者和 SKM-1 细胞中 PRKCQ-AS1 的表达和特征。

结果

生物信息学分析显示，与 DNMT 相关的 DE-lncRNA PRKCQ-AS1 与 DNA 甲基化功能相关。与 DNA 甲基化相关的 PRKCQ-AS1 的靶基因主要是蛋氨酸合成酶（MTR）和 ten-eleven-translocation 1（TET1）。此外，在真实的 MDS 病例中验证了 PRKCQ-AS1 的高表达。在 SKM-1 细胞中的进一步细胞分析表明，过表达的 PRKCQ-AS1 促进了长散布核元件 1（LINE-1）和细胞增殖的甲基化水平，明显提高了 MTR 和 TET1 的 mRNA 和蛋白水平，而 PRKCQ-AS1 的敲低在 SKM-1 细胞中则表现出相反的趋势。