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采用全基因组基因表达谱筛选结直肠癌相关基因。

Screening for implicated genes in colorectal cancer using whole‑genome gene expression profiling.

机构信息

Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.

出版信息

Mol Med Rep. 2018 Jun;17(6):8260-8268. doi: 10.3892/mmr.2018.8862. Epub 2018 Apr 11.

Abstract

To identify biologically relevant genes associated with the pathogenesis of colorectal cancer (CRC), genome wide expression profiles of 17 pairs of CRC tumor and adjacent tissues, previously published in a DNA microarray study, were analyzed. Cytoscape, String tools and DAVID tools were used to investigate the biological pathways encoded by the genes identified as being either upregulated or downregulated in CRC, to determine protein‑protein interactions and to identify potential hub genes associated with CRC. As a result, a total of 3,264 genes were identified as being differentially expressed in CRC and adjacent tissues, including 1,594 downregulated and 1,670 upregulated genes. Furthermore, 306 genes were revealed to be clustered in a complex interaction network, and the top 20 hub genes in this network were determined by application of the Matthews Correlation Coefficient algorithm. In addition, the patterns of the expression levels of the 20 hub genes were investigated using reverse transcription‑quantitative polymerase chain reaction. Gene Ontology analysis revealed that four of the 20 hub genes encoded small subunit processome components (UTP3 small subunit processome component; UTP14 small subunit processome component; UTP 18 small subunit processome component; and UTP20 small subunit processome component) and a further four encoded WD repeat domains (WD repeat‑containing protein 3, WD repeat domain 12, WD repeat‑containing protein 43 and WD repeat‑containing protein 75). In conclusion, the present DNA microarray study identified genes involved in the pathogenesis of CRC. Furthermore, it was revealed that hub genes identified from among the total identified upregulated and downregulated genes in CRC encoding subunit processome components and WD repeat domains may represent novel target molecules for future treatments of CRC.

摘要

为了鉴定与结直肠癌(CRC)发病机制相关的生物学上有意义的基因,我们对之前在 DNA 微阵列研究中发表的 17 对 CRC 肿瘤组织和相邻组织的全基因组表达谱进行了分析。我们使用 Cytoscape、String tools 和 DAVID tools 来研究被鉴定为在 CRC 中上调或下调的基因所编码的生物途径,确定蛋白质-蛋白质相互作用,并鉴定与 CRC 相关的潜在核心基因。结果,共鉴定出 3264 个在 CRC 和相邻组织中差异表达的基因,包括 1594 个下调基因和 1670 个上调基因。此外,有 306 个基因被揭示聚类在一个复杂的相互作用网络中,通过应用 Matthews 相关系数算法确定了该网络中的前 20 个核心基因。此外,还通过逆转录-定量聚合酶链反应研究了这 20 个核心基因的表达水平模式。基因本体论分析显示,这 20 个核心基因中有 4 个编码小亚基核糖体成分(UTP3 小亚基核糖体成分;UTP14 小亚基核糖体成分;UTP18 小亚基核糖体成分;和 UTP20 小亚基核糖体成分),另外 4 个编码 WD 重复结构域(WD 重复含蛋白 3、WD 重复域 12、WD 重复含蛋白 43 和 WD 重复含蛋白 75)。综上所述,本 DNA 微阵列研究鉴定了参与 CRC 发病机制的基因。此外,研究结果还表明,从 CRC 中总鉴定出的上调和下调基因中识别出的核心基因,编码亚基核糖体成分和 WD 重复结构域,可能代表未来 CRC 治疗的新的靶分子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d337/5984002/920a7b2c08ee/MMR-17-06-8260-g00.jpg

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