| 沈凝香,罗鸣宇,顾玮铭,张墨聪,沈 瑛.谷胱甘肽转移酶ω1基于酶活位点调控波形蛋白表达并促进肺腺癌恶性进展[J].,2024,(2):201-205 |
| 谷胱甘肽转移酶ω1基于酶活位点调控波形蛋白表达并促进肺腺癌恶性进展 |
| Glutathione S-Transferase Omega 1 Regulates Vimentin Expression Based on Active Site and Promote Malignancy of Lung Adenocarcinoma |
| 投稿时间：2023-08-15 修订日期：2023-08-31 |
| DOI：10.13241/j.cnki.pmb.2024.02.001 |
| 中文关键词: 谷胱甘肽转移酶ω1 波形蛋白 肺腺癌 |
| 英文关键词: Glutathione S-Transferase Omega 1 Vimentin Lung adenocarcinoma |
| 基金项目:上海市高水平地方高校建设项目--药学学科（PT21010） |
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| 中文摘要: |
| 摘要 目的：探究谷胱甘肽转移酶ω1（Glutathione S-Transferase Omega 1, GSTO1）关键酶活位点Cys32与肺腺癌恶性进展的关系与初步作用机制。方法：构建GSTO1野生型与酶活失活点突变C32A型过表达的肺腺癌细胞系，观察过表达细胞的形态变化及增殖能力的变化。以临床数据生物信息学分析探究GSTO1调控的促肿瘤蛋白，使用免疫印迹法验证该蛋白在GSTO1野生型与酶活失活点突变C32A型过表达的肺腺癌细胞系中的表达差异，并结合临床公共数据库分析该蛋白与患者预后的关联。结果：发现过表达野生型GSTO1能够引起肺腺癌细胞PC9的形态变化并促进PC9细胞增殖，而过表达C32A突变型GSTO1的PC9细胞与空载体组细胞形态及增殖能力相似；临床数据提示GSTO1与波形蛋白（Vimentin, VIM）表达呈现正相关，免疫印迹法显示野生型GSTO1过表达能够引起Vimentin蛋白表达上调，而C32A酶活失活点突变型GSTO1过表达无法引起Vimentin蛋白表达上调；通过临床样本数据观察GSTO1与Vimentin共同高表达的肺腺癌患者肿瘤恶性程度更高、发生转移的比例更大，同时无病生存期与总生存期更短。结论：GSTO1基于其酶活位点调控Vimentin表达，改变肺腺癌细胞形态并促进肺腺癌细胞增殖，研究结果为靶向GSTO1的肺腺癌治疗提供了新思路。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the relationship between key activity site Cys32 of Glutathione S-Transferase Omega 1 (GSTO1) and malignant progression of lung adenocarcinoma, and to clarify the potential mechanism. Methods: Wild-type (GSTO1 WT ) and inactivation mutant GSTO1 (GSTO1 C32A ) were overexpressed in lung adenocarcinoma PC9 cells by lentivirus packaging and infection system. Western blot assay was used to verify whether the model was constructed successfully. Cell morphology was investigated by inverted phase-contrast microscopy. CCK8 assay and clonogenic assay were performed to detect cell proliferation. Clinical data mining was used to explore the cancer-promoting protein regulated by GSTO1, and western blot assay was performed to verify protein levels in GSTO1 WT and GSTO1 C32A overexpressed lung adenocarcinoma cell lines. Correlation between expression levels and clinical stage, differentiation, metastasis, and survival of lung adenocarcinoma patients using clinical databases. Results: Morphological changes of lung adenocarcinoma cells was induced by GSTO1 WT instead of GSTO1 C32A overexpression. Comparing with GSTO1 C32A overexpression and empty vehicle group, GSTO1 WT overexpression promoted the proliferation of PC9 cells. Clinical data suggested that there was a positive correlation between the expression of GSTO1 and vimentin (VIM), and western blot assay showed that the overexpression of GSTO1 WT upregulated protein level of vimentin, while GSTO1 C32A overexpression not. Clinical data mining showed that lung adenocarcinoma patients with high co-expression of GSTO1 and vimentin were associated with a greater degree of tumor malignancy and a higher proportion of metastasis, as well as shorter disease-free survival and overall survival. Conclusion: The GSTO1 regulates expression of vimentin based on its enzyme-active site and promote the malignancy of lung adenocarcinoma, which indicates that GSTO1 was a potential metabolic vulnerability in lung adenocarcinoma. |
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