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G9A通过上调其靶标在乳腺癌进展中发挥重要作用。

G9A performs important roles in the progression of breast cancer through upregulating its targets.

作者信息

Jiang Wenhua, Liu Pengfei, Li Xiaodong

机构信息

Department of Radiotherapy, Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.

Department of Lymphoma, Sino-US Center of Lymphoma and Leukemia, Tianjin Medical University Cancer Institute and Hospital, Tianjin's National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China.

出版信息

Oncol Lett. 2017 Jun;13(6):4127-4132. doi: 10.3892/ol.2017.5977. Epub 2017 Apr 3.

Abstract

Breast cancer (BC) is the most common type of malignancy in females worldwide, however, its underlying mechanisms remain poorly understood. The present study aimed to investigate the mechanisms behind the development and progression of BC and identify potential biomarkers for it. The chromatin immunoprecipitation-DNA sequencing (ChIP-Seq) dataset GSM1642516 and gene expression dataset GSE34925 were downloaded from the Gene Expression Omnibus database. Affy and oligo packages were used for the background correction and normalization of the gene expression dataset. Based on Limma package and the criteria of a fold change >1.41 or <0.71, and a false discovery rate adjusted P-value <0.05, differentially-expressed genes (DEGs) in euchromatic histone lysine methyltransferase 2 () -knockout (KO) breast samples compared with control samples were identified. The Database for Annotation, Visualization and Integrated Analysis was used for the functional enrichment analysis of the DEGs. Bowtie 2 and model-based analysis of ChIP-Seq version 14 (macs14) were used for the mapping of raw reads and the identification of G9A binding sites (peaks), respectively. In addition, overlapping genes between the DEGs and genes in the peaks located in -3000 to 3000 bp centered in the transcription start sites (conpeaks) were screened out and microRNAs (miRNAs) believed to regulate those overlaps were identified through the TargetScan database. A total of 217 DEGs were identified in G9A-KO samples, which were mainly involved in the biological processes and pathways associated with the inflammatory response and cancer progression. A total of 10,422 peaks, containing 1,210 conpeaks involving 1,138 genes, were identified. Among the 1,138 genes, 15 were overlapped with the DEGs, and 35 miRNAs were identified to regulate those overlaps. Insulin-induced gene 1 was regulated by 9 genes in the miRNA-gene regulation network, which may indicate its importance in the progression of BC. The present study identified potential biomarkers of BC that may be useful in the diagnosis and treatment of patients with the disease.

摘要

乳腺癌(BC)是全球女性中最常见的恶性肿瘤类型,然而,其潜在机制仍知之甚少。本研究旨在探讨BC发生和发展背后的机制,并确定其潜在的生物标志物。从基因表达综合数据库下载了染色质免疫沉淀- DNA测序(ChIP-Seq)数据集GSM1642516和基因表达数据集GSE34925。使用Affy和oligo软件包对基因表达数据集进行背景校正和标准化。基于Limma软件包以及倍数变化>1.41或<0.71且错误发现率调整后的P值<0.05的标准,鉴定了常染色质组蛋白赖氨酸甲基转移酶2()基因敲除(KO)乳腺样本与对照样本相比的差异表达基因(DEG)。使用注释、可视化和综合分析数据库对DEG进行功能富集分析。分别使用Bowtie 2和基于模型的ChIP-Seq版本14(macs14)对原始读数进行映射和鉴定G9A结合位点(峰)。此外,筛选出DEG与位于转录起始位点中心-3000至3000 bp处峰中的基因之间的重叠基因,并通过TargetScan数据库鉴定被认为调节这些重叠的微小RNA(miRNA)。在G9A-KO样本中总共鉴定出217个DEG,它们主要参与与炎症反应和癌症进展相关的生物学过程和途径。总共鉴定出10422个峰,其中包含1210个涉及1138个基因的共峰。在这1138个基因中,有15个与DEG重叠,并鉴定出35个miRNA调节这些重叠。胰岛素诱导基因1在miRNA-基因调控网络中受9个基因调控,这可能表明其在BC进展中的重要性。本研究确定了BC的潜在生物标志物,可能对该疾病患者的诊断和治疗有用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e0a/5453034/a67e793abd1d/ol-13-06-4127-g00.jpg

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