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

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.

Unveiling the gene regulatory landscape in diseases through the identification of DNase I‑hypersensitive sites (Review)

“…The inhibitor of DNA-binding 1 HLH protein (ID1) is the only transcription factor that is significantly upregulated, exhibiting basal sequence enrichment in the promoter region of the upregulated gene. Therefore, CTCF, ELK1 and ID1 may be potential targets for the treatment of prostate cancer (60). Increasing evidence shows that changes in the expression of BMP4 are involved in the pathogenesis of cancer, which is associated with cancer metastasis and progression, including rectal, hepatocellular and ovarian cancer (61).…”

Combined analysis of chromatin accessibility and gene expression profiles provide insight into Fucoxanthin biosynthesis in Isochrysis galbana under green light

“…An assay for transposase accessible chromatin sequencing (ATACseq) is an efficient technology used to study genome-wide open chromatin region accessibility by investigating chromatin status and identifying transcription factor binding sites. This technique is popular because of its simple operation, time-saving, strong repeatability, and low material input compared to ChIP-seq, DNAse-seq, and FAIRE-seq (Wei et al, 2018;Sen et al, 2021Sen et al, , 2022. Although ATAC-seq has been used successfully in Arabidopsis thaliana, Vitis amurensis, embryonic cells, and tumors, there is little research on chromatin accessibility for gene expression in algae (Corces et al, 2018;Del Priore et al, 2021;Farmer et al, 2021;Ren et al, 2021).…”