Epigenetic interplay between methylation and miRNA in bladder cancer: focus on isoform expression

BMC Genomics

卷:22

Research

Seonggyun Han¹  Younghee Lee²  Manu Shivakumar³  Dokyoon Kim³ 

[1] Department of Biomedical Informatics, University of Utah School of Medicine, Salt Lake City, USA;

[2] Department of Biomedical Informatics, University of Utah School of Medicine, Salt Lake City, USA;Huntsman Cancer Institute, Salt Lake City, USA;

[3] Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA;Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, PA, USA;

关键词: Epigenetics;    Bladder cancer;    Methylation;    miRNA;    Isoform expression;   

DOI  :  10.1186/s12864-021-08052-9

 received in 2021-09-20, accepted in 2021-09-24,  发布年份 2021

来源: Springer

【 摘 要 】

BackgroundVarious epigenetic factors are responsible for the non-genetic regulation on gene expression. The epigenetically dysregulated oncogenes or tumor suppressors by miRNA and/or DNA methylation are often observed in cancer cells. Each of these epigenetic regulators has been studied well in cancer progressions; however, their mutual regulatory relationship in cancer still remains unclear. In this study, we propose an integrative framework to systematically investigate epigenetic interactions between miRNA and methylation at the alternatively spliced mRNA level in bladder cancer. Each of these epigenetic regulators has been studied well in cancer progressions; however, their mutual regulatory relationship in cancer still remains unclear.ResultsThe integrative analyses yielded 136 significant combinations (methylation, miRNA and isoform). Further, overall survival analysis on the 136 combinations based on methylation and miRNA, high and low expression groups resulted in 13 combinations associated with survival. Additionally, different interaction patterns were examined.ConclusionsOur study provides a higher resolution of molecular insight into the crosstalk between two epigenetic factors, DNA methylation and miRNA. Given the importance of epigenetic interactions and alternative splicing in cancer, it is timely to identify and understand the underlying mechanisms based on epigenetic markers and their interactions in cancer, leading to alternative splicing with primary functional impact.

【 授权许可】

CC BY   
© The Author(s) 2021

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