Title:Comprehensive DNA Methylation-transcriptome Profiles Association Analysis During the Treatment of Acute Myelocytic Leukemia
Volume: 27
Issue: 24
Author(s): Jun Wu, Ming-Zhu Song, Li-Jun Deng and Qian-Ling Ye*
Affiliation:
- Department of Hematology, the Second Affiliated Hospital of Anhui Medical University, Hefei,China
Keywords:
Epigenetics, DNA methylation, acute myelocytic leukemia, ceRNAs, lncRNAs, stem cell.
Abstract:
Background: Epigenetic modifications have recently attracted much attention in the study of the biological
mechanisms of Acute Myelocytic Leukemia (AML) for therapy and prognosis. However, studies on
DNA methylation changes during AML treatment are limited.
Objective: The comprehensive DNA methylation-transcriptome profiles association analysis in this study
aimed to establish whole-genome DNA methylation profiles and explore DNA methylation-related genes and
their potential functions before and after treatment. And more appropriate biomarkers are expected to be identified
for therapy strategies in AML.
Methods: Illumina 450K and RNA-Seq data were obtained from the Cancer Genome Atlas. We performed comprehensive
DNA methylation-transcriptome profiles association analysis, pathway analysis, correlation analysis,
and survival analyses. The StarBase database was utilized to predict interactions between lncRNAs, miRNAs
and target mRNAs.
Results: In total, 1592 distinct CpG sites and 2419 different expression transcripts were identified between pretreatment
and post-treatment AML. The significantly enriched functions of methylated genes were stem cell differentiation,
cell population maintenance, and cell development. The expression of UGT3A2, MOG, and VSTM1
was correlated with DNA methylation levels (r2
>0.5). Lastly, we identified 4 lncRNAs, 9 miRNAs and 142
mRNAs to construct a lncRNA-miRNA-mRNA ceRNA network.
Conclusion: Our results revealed that DNA methylation was altered before and after treatment. Alterations in
DNA methylation affected target gene expression and participated in the key biological processes of AML.
Therefore, ceRNA networks may provide further insight into the study of favorable therapeutic markers in
AML.
