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BMC Med Genomics. 2017 May 24;10(Suppl 1):30. doi: 10.1186/s12920-017-0269-y.

Identification of epigenetic interactions between miRNA and DNA methylation associated with gene expression as potential prognostic markers in bladder cancer.

Author information

1
Biomedical & Translational Informatics Institute, Geisinger Health System, Danville, PA, USA.
2
Department of Biomedical Informatics, University of Utah School of Medicine, Salt Lake City, UT, USA.
3
Mowad Urology Department, Geisinger Health System, Danville, PA, USA.
4
Department of Software and Computer Engineering, Ajou University, Suwon, South Korea. kasohn@ajoun.ac.kr.
5
Biomedical & Translational Informatics Institute, Geisinger Health System, Danville, PA, USA. dkim@geisinger.edu.
6
The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, USA. dkim@geisinger.edu.

Abstract

BACKGROUND:

One of the fundamental challenges in cancer is to detect the regulators of gene expression changes during cancer progression. Through transcriptional silencing of critical cancer-related genes, epigenetic change such as DNA methylation plays a crucial role in cancer. In addition, miRNA, another major component of epigenome, is also a regulator at the post-transcriptional levels that modulate transcriptome changes. However, a mechanistic role of synergistic interactions between DNA methylation and miRNA as epigenetic regulators on transcriptomic changes and its association with clinical outcomes such as survival have remained largely unexplored in cancer.

METHODS:

In this study, we propose an integrative framework to identify epigenetic interactions between methylation and miRNA associated with transcriptomic changes. To test the utility of the proposed framework, the bladder cancer data set, including DNA methylation, miRNA expression, and gene expression data, from The Cancer Genome Atlas (TCGA) was analyzed for this study.

RESULTS:

First, we found 120 genes associated with interactions between the two epigenomic components. Then, 11 significant epigenetic interactions between miRNA and methylation, which target E2F3, CCND1, UTP6, CDADC1, SLC35E3, METRNL, TPCN2, NACC2, VGLL4, and PTEN, were found to be associated with survival. To this end, exploration of TCGA bladder cancer data identified epigenetic interactions that are associated with survival as potential prognostic markers in bladder cancer.

CONCLUSIONS:

Given the importance and prevalence of these interactions of epigenetic events in bladder cancer it is timely to understand further how different epigenetic components interact and influence each other.

KEYWORDS:

Bladder cancer; Integrative analysis; Interaction between miRNA and methylation; TCGA

PMID:
28589857
PMCID:
PMC5461531
DOI:
10.1186/s12920-017-0269-y
[Indexed for MEDLINE]
Free PMC Article

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