| 摘要: |
| 目的 分析G蛋白亚基Alpha O1(G protein subunit alpha O1,GNAO1)在脑胶质瘤中的表达情况并对预后的影响,研究GNAO1表达对脑胶质瘤细胞上皮-间质转化、细胞增殖、迁移和侵袭的作用。方法 利用临床样本组织芯片和TCGA数据库对脑胶质瘤中GNAO1的表达情况、临床特征相关性及对生存预后的影响进行分析。通过基因功能富集分析和蛋白相互作用分析预测GNAO1在脑胶质瘤中的作用。通过在脑胶质瘤细胞(U-87MG和U251)中稳定过表达GNAO1,利用细胞增殖实验、划痕实验和Transwell实验检测GNAO1表达对脑胶质瘤细胞增殖、迁移和侵袭能力的影响。通过蛋白免疫印迹检测上皮-间质转化相关分子标志物N-cadherin、E-cadherin、β-catenin、α-SMA、MMP-2、MMP-9的表达情况,确证GNAO1表达对脑胶质瘤细胞上皮-间质转化的影响。结果 临床样本和TCGA数据库分析结果表明GNAO1在脑胶质瘤中低表达并与患者不良预后相关。GO/KEGG功能富集分析结果表明GNAO1表达与细胞增殖、迁移和侵袭能力相关。蛋白相互作用及共表达预后分析表明GNAO1与GABBR1、ZBTB16和FZD家族等分子共同参与调节脑胶质瘤预后。在细胞学水平,过表达GNAO1可通过抑制N-cadherin和促进E-cadherin表达来抑制脑胶质瘤细胞的上皮-间质转化过程,进而抑制U-87MG和U251细胞的增殖、迁移和侵袭能力。结论 GNAO1在脑胶质瘤中低表达并与脑胶质瘤患者预后不良相关,在体外通过促进上皮-间质转化过程来促进脑胶质瘤细胞的增殖、迁移和侵袭能力。 |
| 关键词: 脑胶质瘤 G蛋白亚基Alpha O1 上皮-间质转化 迁移 侵袭 |
| DOI： |
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| 基金项目:浙江省自然科学(No.LQ23H160008)；浙江省自然科学基金重点项目(No. LZ20H290001) |
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| The downregulation of GNAO1 promotes epithelial-mesenchymal transition and contributes to poor prognosis in glioma |
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LIU Xue1, WU Hui2, WU Qiong3, YAO Qinghua1,4
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1.Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital);2.The Second Clinical Medicine Faculty of Zhejiang Chinese Medical University;3.Integrated Traditional Chinese and Western Medicine Oncology Laboratory, Zhejiang Cancer Hospital;4.The Second Affiliated Hospital of Zhejiang Chinese Medical University, Xinhua Hospital of Zhejiang Province
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| Abstract: |
| Objectives To analyze the expression of G protein subunit alpha O1 (GNAO1) in glioma and its impact on prognosis, as well as investigate the effects of GNAO1 expression on epithelial-mesenchymal transition (EMT), cell proliferation, migration, and invasion in glioma. Methods Clinical samples tissue microarrays and data from the TCGA database were utilized to analyze the expression of GNAO1 in glioma, its correlation with clinical characteristics, and survival prognosis. Gene ontology enrichment analysis and protein-protein interaction analysis were employed to predict the role of GNAO1 in glioma. GNAO1 was consistently upregulated in glioma cells (U-87MG and U251), and its effects on the proliferation, migration, and invasion of these cells were evaluated through cell proliferation assays, scratch assays, and Transwell assays. Western Blot analysis was utilized to investigate the expression levels of epithelial-mesenchymal transition (EMT) markers such as N-cadherin, E-cadherin, β-catenin, α-SMA, MMP-2, and MMP-9, in order to explore the impact of GNAO1 on EMT in glioma cells. Results Examination of clinical specimens and the Cancer Genome Atlas (TCGA) database demonstrates a reduction in GNAO1 expression in glioma, which is linked to unfavorable patient outcomes. Functional enrichment analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways reveals a correlation between GNAO1 levels and the proliferation, migration, and invasion capacities of cells. Additionally, protein-protein interaction and co-expression prognosis analyses suggest that GNAO1, in conjunction with molecules such as GABBR1, ZBTB16, and members of the FZD family, collectively contribute to the regulation of glioma prognosis. At the cellular level, the upregulation of GNAO1 has been shown to impede epithelial-mesenchymal transition (EMT) in glioma cells through the downregulation of N-cadherin and upregulation of E-cadherin, resulting in the inhibition of proliferation, migration, and invasion capabilities in U-87 MG and U251 cells. Conclusion GNAO1 exhibits decreased expression levels in glioma, correlating with unfavorable prognostic outcomes in patients with this disease. In vitro studies demonstrate that GNAO1 facilitates glioma cell proliferation, migration, and invasion by augmenting EMT. |
| Key words: Glioma G protein subunit alpha O1 Epithelial–Mesenchymal Transition Migration Invasion |