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加权基因共表达网络分析和预后分析鉴定与头颈部鳞状细胞癌相关的枢纽基因和分子机制。

Weighted gene co-expression network analysis and prognostic analysis identifies hub genes and the molecular mechanism related to head and neck squamous cell carcinoma.

机构信息

a Department of Head and Neck Surgery , Sun Yat-sen University Cancer Center , Guangzhou , Guangdong , China.

b State Key Laboratory of Oncology in South China , Guangzhou , Guangdong , China.

出版信息

Cancer Biol Ther. 2019;20(6):750-759. doi: 10.1080/15384047.2018.1564560. Epub 2019 Mar 22.

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a lethal disease with suboptimal survival outcomes. In this study, we aimed to find an independent prognostic factor of head and neck squamous cell carcinoma and investigate its effect on tumor cell proliferation, apoptosis, migration progress and cell cycle phase. Weighted gene co-expression network analysis (WGCNA) is an analysis method for mining module information in chip data through soft threshold. In this article, it was used to divide differential genes into different modules and determined the ten hub genes. Overall survival (OS) and disease-free survival (DFS) analyses as well as univariate and multivariate regression analyses were used to figure out HMGA2 as the independent prognostic factor. RT-qPCR and western blot results revealed the HMGA2 expression levels. Via colony formation, flow cytometry and wound healing assays, we tested the involvement of HMGA2 knockdown in corresponding cancer cell biological behaviors. HMGA2 level was up-regulated in HNSCC tissues and cell lines (SCC-25 and FaDu) in comparison with their normal counterparts. HMGA2 knockdown decreased cancer cell proliferation, promoted cell apoptosis, blocked cell cycle at G0/G1 phase, and inhibited cell migration. We regarded HMGA2 as a potential diagnostic and therapeutic target of HNSCC.

摘要

头颈部鳞状细胞癌(HNSCC)是一种致命疾病,其生存结局不佳。在本研究中,我们旨在寻找头颈部鳞状细胞癌的独立预后因素,并研究其对肿瘤细胞增殖、凋亡、迁移进展和细胞周期阶段的影响。加权基因共表达网络分析(WGCNA)是一种通过软阈值挖掘芯片数据中模块信息的分析方法。在本文中,它被用于将差异基因分为不同的模块,并确定了十个枢纽基因。总生存(OS)和无病生存(DFS)分析以及单变量和多变量回归分析用于确定 HMGA2 是独立的预后因素。RT-qPCR 和 Western blot 结果显示了 HMGA2 的表达水平。通过集落形成、流式细胞术和划痕愈合实验,我们测试了 HMGA2 敲低在相应癌细胞生物学行为中的参与情况。与正常对照相比,HMGA2 在 HNSCC 组织和细胞系(SCC-25 和 FaDu)中上调。HMGA2 敲低降低了癌细胞的增殖能力,促进了细胞凋亡,阻止了细胞周期在 G0/G1 期,并抑制了细胞迁移。我们认为 HMGA2 是 HNSCC 的一个潜在的诊断和治疗靶点。

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