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通过整合分析 DNase-seq 和 RNA-seq 数据鉴定前列腺癌中的开放染色质区域和关键基因。

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

机构信息

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.

出版信息

Mol Med Rep. 2018 Aug;18(2):2245-2252. doi: 10.3892/mmr.2018.9193. Epub 2018 Jun 19.

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.

摘要

前列腺癌是一种起源于前列腺外周带的腺癌,目前可用的治疗方法无法治愈转移性前列腺癌。本研究旨在鉴定与前列腺癌发展相关的开放染色质区域和差异表达基因(DEGs)。从基因表达综合数据库中下载了 DNase 测序数据(GSE33216)和 RNA 测序数据(GSE22260)。检测并分析了 DNase I 超敏位点。随后,鉴定了差异表达基因,并对其潜在功能进行了富集。最后,预测了 DEGs 的上游调控元件。在 LNCaP 细胞中,雄激素受体激活后,鉴定到 244 个上调和 486 个下调的开放染色质区域。然而,仅有 1%的开放染色质区域发生动态改变。在其启动子区域具有上调的开放染色质信号的 41 个基因主要富集在生物学过程中。此外,在前列腺癌中鉴定到 211 个上调和 150 个下调的 DEGs,其中包括 8 个转录因子(TFs)。最后,预测到 9 个与前列腺癌相关的调控元件。特别是,DNA 结合抑制因子 1 螺旋环螺旋蛋白(ID1)是唯一显著上调的 TF,其在上调基因的启动子区域表现出基序富集。富集在下调基因的开放启动子区域的结合蛋白 1(CTCF)和 Elk1 ETS 转录因子(ELK1)是潜在的上游调控元件。此外,反转录定量聚合酶链反应分析证实,与 BPH1 细胞相比,ID1 在 LNCaP 细胞和 5α-二氢睾酮(DHT)处理的 LNCaP 细胞中表达显著上调,而 CTCF 和 ELK1 在 LNCaP 细胞和 DHT 处理的 LNCaP 细胞中表达显著下调。总之,ID1、CTCF 和 ELK1 可能与前列腺癌相关,可能是治疗该疾病的潜在治疗靶点。

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