An Integrated Regulatory Network Based on Comprehensive Analysis of mRNA Expression, Gene Methylation and Expression of Long Non-coding RNAs (lncRNAs) in Myelodysplastic Syndromes
An Integrated Regulatory Network Based on Comprehensive Analysis of mRNA Expression, Gene Methylation and Expression of Long Non-coding RNAs (lncRNAs) in Myelodysplastic Syndromes
复制标题
基于骨髓增生异常综合征中 mRNA 表达、基因甲基化和长非编码 RNA (lncRNA) 表达综合分析的综合调控网络
DOI：
10.3389/fonc.2019.00200
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发表时间：
2019-03-29
影响因子：
4.7
通讯作者：
Wang, Xiaoqin
中科院分区：
文献类型：
--
作者：
Zhao, Xiaoli;Yin, Hua;Wang, Xiaoqin
骨髓增生异常综合征（MDS）是一组异质性疾病，其特征在于无效造血、造血前体细胞分化缺陷和异常克隆扩增。MDS的发病率已引起世界各国的高度关注，但其发病机制仍不清楚。为了提供关于诊断和治疗MDS的新型生物标志物的见解，我们对四名MDS患者和四名年龄匹配的骨髓进行了高通量全基因组mRNA表达谱分析、DNA甲基化分析和长链非编码RNA（lncRNA）分析。健康对照。我们鉴定了1，937个差异表达基因（DEG），515个甲基化基因和214个lncRNA，显示出统计学显著差异。作为最重要的模块相关的DEG，TCL1A，PTGS 2和MME被揭示富集在细胞分化和细胞死亡途径的调节中。此外，由顶级DEG鉴定的GeneGo通路图谱显示出在癌症、免疫调节、细胞凋亡和肌动蛋白细胞骨架调节方面的收敛，其中大多数是MDS病因学和发病机制的已知贡献者。值得注意的是，作为用于诊断MDS的潜在生物标志物，对四个特定基因（ABAT、FADD、DAPP 1和SMPD 3）进一步进行详细的途径分析。本研究对MDS的mRNA表达、基因甲基化和lncRNA谱的综合分析有助于进一步了解MDS的发病机制，为MDS的诊断和治疗提供新的思路。
Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by ineffective hematopoiesis, defective differentiation of hematopoietic precursors, and expansion of the abnormal clones. The prevalence of MDS has raised great concerns worldwide, but its pathogenetic mechanisms remain elusive. To provide insights on novel biomarkers for the diagnosis and therapy of MDS, we performed high-throughput genome-wide mRNA expression profiling, DNA methylation analysis, and long non-coding RNAs (lncRNA) analysis on bone marrows from four MDS patients and four age-matched healthy controls. We identified 1,937 differentially expressed genes (DEGs), 515 methylated genes, and 214 lncRNA that showed statistically significant differences. As the most significant module-related DEGs, TCL1A, PTGS2, and MME were revealed to be enriched in regulation of cell differentiation and cell death pathways. In addition, the GeneGo pathway maps identified by top DEGs were shown to converge on cancer, immunoregulation, apoptosis and regulation of actin cytoskeleton, most of which are known contributors in MDS etiology and pathogenesis. Notably, as potential biomarkers for diagnosis of MDS, four specific genes (ABAT, FADD, DAPP1, and SMPD3) were further subjected to detailed pathway analysis. Our integrative analysis on mRNA expression, gene methylation and lncRNAs profiling facilitates further understanding of the pathogenesis of MDS, and may promote the diagnosis and novel therapeutics for this disease.