Identification of open chromosomal regions and key genes in prostate cancer via integrated analysis of DNase‑seq and RNA‑seq data

Wei,Xin; Yu,Lili; Jin,Xuefei; Song,Lide; Lv,Yanting; Han,Yuping

doi:10.3892/mmr.2018.9193

Identification of open chromosomal regions and key genes in prostate cancer via integrated analysis of DNase‑seq and RNA‑seq data

Authors:
- Xin Wei
- Lili Yu
- Xuefei Jin
- Lide Song
- Yanting Lv
- Yuping Han
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Affiliations: Department of Urology, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China, Department of Radiology, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China, Department of Pathology, Zhuji People's Hospital, Zhuji, Zhejiang 311800, P.R. China
Published online on: June 19, 2018 https://doi.org/10.3892/mmr.2018.9193
Pages: 2245-2252

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Abstract

Prostate cancer is a type of adenocarcinoma arising from the peripheral zone of the prostate gland, and metastasized prostate cancer is incurable with the current available therapies. The present study aimed to identify open chromosomal regions and differentially expressed genes (DEGs) associated with prostate cancer development. The DNase sequencing data (GSE33216) and RNA sequencing data (GSE22260) were downloaded from the Gene Expression Omnibus database. DNase I hypersensitive sites were detected and analyzed. Subsequently, DEGs were identified and their potential functions were enriched. Finally, upstream regulatory elements of DEGs were predicted. In LNCaP cells, following androgen receptor activation, 244 upregulated and 486 downregulated open chromosomal regions were identified. However, only 1% of the open chromosomal regions were dynamically altered. The 41 genes with upregulated open chromosomal signals within their promoter regions were primarily enriched in biological processes. Additionally, 211 upregulated and 150 downregulated DEGs were identified in prostate cancer, including eight transcription factors (TFs). Finally, nine regulatory elements associated with prostate cancer were predicted. In particular, inhibitor of DNA binding 1 HLH protein (ID1) was the only significantly upregulated TF which exhibited motif enrichment in the promoter regions of upregulated genes. CCCTC‑binding factor (CTCF) and ELK1 ETS transcription factor (ELK1), enriched in the open promoter regions of downregulated genes, were potential upstream regulatory elements. Furthermore, reverse transcription‑quantitative polymerase chain reaction analysis confirmed that ID1 expression was significantly upregulated in LNCaP cells and 5α‑dihydrotestosterone (DHT)‑treated LNCaP cells compared with that in BPH1 cells, while CTCF and ELK1 expression was significantly downregulated in LNCaP cells and DHT‑treated LNCaP cells. In conclusion, ID1, CTCF and ELK1 may be associated with prostate cancer, and may be potential therapeutic targets for the treatment of this disease.

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