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Genes 2018, 9(1), 32; doi:10.3390/genes9010032

Genome-Wide Methylation Patterns in Androgen-Independent Prostate Cancer Cells: A Comprehensive Analysis Combining MeDIP-Bisulfite, RNA, and microRNA Sequencing Data

Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, ShangCai Village, Ouhai District of Wenzhou, Wenzhou 325000, China
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Received: 30 November 2017 / Revised: 21 December 2017 / Accepted: 30 December 2017 / Published: 11 January 2018
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Abstract

This study aimed to investigate the mechanisms underlying the development of the androgen-independent phenotype in prostate cancer. Methylation patterns were detected in androgen-independent and androgen-dependent lymph node carcinoma of the prostate (LNCaP) prostate carcinoma cells based on methylated DNA immunoprecipitation-bisulfite sequencing data and differentially methylated regions (DMRs) were identified. Differentially expressed genes (DEGs) and micro RNAs (miRNAs) with DMRs (named MDEGs and MDEmiRNAs) were identified by combining transcriptome and methylation data, and transcription factor (TF)-DEGs with DMRs in promoter (PMDEGs) and MDEmiRNA-MDEGs networks were constructed. Furthermore, a time-course analysis of gene transcription during androgen deprivation was performed based on microarray data and DMRs, MDEGs, and DEmiRNAs were validated. In total, 18,447 DMRs, 3369 MDEGs, 850 PMDEGs, and 1 MDEmiRNA (miR-429) were identified. A TF-target network (94 PMDEGs and 5 TFs) and a miRNA–target network (172 MDEGs and miR-429) were constructed. Based on the time-course analysis of genes in the networks, NEDD4L and PBX3 were targeted by SOX5, while GNAQ, ANLN, and KIF11 were targeted by miR-429. The expression levels of these genes and miR-429 were confirmed by quantitative real-time polymerase chain reaction. Additionally, 109 DMRs were confirmed using additional public datasets. The regulatory pathways SOX5-NEDD4L/PBX3, miR429-GNAQ/ANLNRHOA, and miR429-ANLNKIF11 may participate in the progression of the androgen-independent phenotype in prostate cancer. View Full-Text
Keywords: androgen-independent; prostate cancer; MeDIP-bisulfite sequencing; microRNA; time-course androgen-independent; prostate cancer; MeDIP-bisulfite sequencing; microRNA; time-course
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Wang, Y.; Qin, T.; Hu, W.; Chen, B.; Dai, M.; Xu, G. Genome-Wide Methylation Patterns in Androgen-Independent Prostate Cancer Cells: A Comprehensive Analysis Combining MeDIP-Bisulfite, RNA, and microRNA Sequencing Data. Genes 2018, 9, 32.

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