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基于生物信息学分析鉴定脑胶质母细胞瘤中的潜在癌基因,并阐明其潜在机制。

Identification of the potential oncogenes in glioblastoma based on bioinformatic analysis and elucidation of the underlying mechanisms.

机构信息

Department of Neurosurgery, The People's Hospital of Guizhou Provincial, Guiyang, Guizhou 550002, P.R. China.

出版信息

Oncol Rep. 2018 Aug;40(2):715-725. doi: 10.3892/or.2018.6483. Epub 2018 Jun 11.

Abstract

Glioblastoma (GBM) is a common malignant tumour in the human brain, but its molecular mechanisms have not been systematically evaluated. The aim of this study was to identify potential key oncogenes associated with the progression of GBM and to elucidate their mechanisms. The gene expression profile of GSE50161, selected from the Gene Expression Omnibus database, was analysed to find cancer‑associated genes and gene functions in GBM. In total, 486 differentially expressed genes, including 128 upregulated genes, were identified. The function and pathway enrichment of these genes were analysed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Survival analysis for three selected partially upregulated genes, CDK1, CCNB1 and CDC20, showed that their high expression was significantly associated with poor survival in GBM. CDK1 was selected for validation of its function and molecular mechanism in GBM. This gene was significantly overexpressed in GBM cancer tissues and cells compared with normal control cells. In addition, knockdown of CDK1 clearly inhibited GBM cell proliferation. Notably, we demonstrated that CDK1 was involved in the Akt signalling pathway, where it promotes the process involved in GBM malignancy.

摘要

胶质母细胞瘤(GBM)是人类大脑中常见的恶性肿瘤,但尚未对其分子机制进行系统评估。本研究旨在鉴定与 GBM 进展相关的潜在关键癌基因,并阐明其机制。从基因表达综合数据库中选择 GSE50161 的基因表达谱,分析 GBM 中的癌症相关基因和基因功能。共鉴定出 486 个差异表达基因,包括 128 个上调基因。通过基因本体论和京都基因与基因组百科全书分析,对这些基因的功能和通路进行了富集分析。对三个选定的部分上调基因(CDK1、CCNB1 和 CDC20)的生存分析表明,其高表达与 GBM 患者的不良预后显著相关。选择 CDK1 来验证其在 GBM 中的功能和分子机制。与正常对照细胞相比,该基因在 GBM 癌组织和细胞中明显过表达。此外,CDK1 的敲低明显抑制了 GBM 细胞的增殖。值得注意的是,我们证明 CDK1 参与了 Akt 信号通路,促进了 GBM 恶性进展过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2844/6072298/a61c2e390f50/OR-40-02-0715-g00.jpg

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