Engrailed 2（EN2）通过抑制肿瘤增殖/侵袭以及增强对替莫唑胺的敏感性来发挥胶质瘤抑制因子的作用。
Engrailed 2 (EN2) acts as a glioma suppressor by inhibiting tumor proliferation/invasion and enhancing sensitivity to temozolomide.
作者信息
Li Tengfei, Yang Wanchun, Li Mao, Zhang Shuxin, Zhou Xingwang, Zuo Mingrong, Yuan Qiuyun, Chen Mina, Liu Yanhui
机构信息
1Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 37 Guoxue Alley, Chengdu, 610041 Sichuan People's Republic of China.
2Neuroscience & Metabolism Research, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 37 Guoxue Alley, Chengdu, 610041 Sichuan People's Republic of China.
出版信息
Cancer Cell Int. 2020 Mar 2;20:65. doi: 10.1186/s12935-020-1145-y. eCollection 2020.
BACKGROUND
Glioma is one of the most malignant brain tumors and accounts for the majority of brain cancer related death. Despite progress on mechanistic studies, current understandings of the initiation and progression of glioma are still incomplete. Previous studies demonstrate that - (EN2), a homeobox-containing transcription factor, is associated with tumorigenesis in a range of cancers heterogeneously, however, the profiles of EN2 expression and its potential functions in gliomas remain unclear.
METHODS
Real-time PCR was used to identify the expression of EN2 in glioma tissues. To study the biological function of EN2 in glioma, we compared the cell viability and proliferation profiles between EN2 overexpressed and control cells using cell counting kit-8 (CCK8) assay, EdU incorporation assay and colony formation assay. Flow cytometry and Hoechst staining assays were performed to investigate the role of EN2 on glioma cell death. Finally, wound healing and transwell assays were carried out to investigate the role of EN2 on glioma cell invasion.
RESULTS
We identified that EN2 was downregulated in human gliomas compared with paired adjacent normal tissues and negatively associated with glioma malignancy. Elevated EN2 expression inhibits cell proliferation, enhances glioma sensitivity to temozolomide and inhibits migration/invasion of glioma cells.
CONCLUSIONS
Our data identify a novel function of EN2 in glioma suppression and provide potential therapeutic targets for glioma therapy.
背景
胶质瘤是最恶性的脑肿瘤之一，占脑癌相关死亡的大多数。尽管在机制研究方面取得了进展，但目前对胶质瘤发生和发展的认识仍然不完整。先前的研究表明，含同源盒的转录因子EN2在一系列癌症的肿瘤发生中存在异质性关联，然而，EN2在胶质瘤中的表达谱及其潜在功能仍不清楚。
方法
采用实时PCR鉴定EN2在胶质瘤组织中的表达。为了研究EN2在胶质瘤中的生物学功能，我们使用细胞计数试剂盒-8（CCK8）检测、EdU掺入检测和集落形成检测比较了EN2过表达细胞和对照细胞之间的细胞活力和增殖情况。进行流式细胞术和Hoechst染色检测以研究EN2对胶质瘤细胞死亡的作用。最后，进行伤口愈合和Transwell检测以研究EN2对胶质瘤细胞侵袭的作用。
结果
我们发现与配对的相邻正常组织相比，EN2在人类胶质瘤中表达下调，并且与胶质瘤恶性程度呈负相关。EN2表达升高可抑制细胞增殖，增强胶质瘤对替莫唑胺的敏感性，并抑制胶质瘤细胞的迁移/侵袭。
结论
我们的数据确定了EN2在胶质瘤抑制中的新功能，并为胶质瘤治疗提供了潜在的治疗靶点。
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