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针对跨膜蛋白97(TMEM97)的RNA干扰抑制胶质瘤细胞的增殖、迁移和侵袭。

RNA interference against TMEM97 inhibits cell proliferation, migration, and invasion in glioma cells.

作者信息

Qiu Guanzhong, Sun Wei, Zou Yongxiang, Cai Zheng, Wang Peng, Lin Xianbin, Huang Jinxiang, Jiang Lei, Ding Xuehua, Hu Guohan

机构信息

Department of Neurosurgery, Shanghai Institute of Neurosurgery, Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China.

Department of Radiology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.

出版信息

Tumour Biol. 2015 Sep;36(10):8231-8. doi: 10.1007/s13277-015-3552-6. Epub 2015 May 23.

Abstract

Gliomas are the most common form of primary brain tumor in the adult central nervous system. Altered expression and prognostic value of transmembrane protein 97 (TMEM97) has been recently reported in different types of human tumors. However, the association of TMEM97and glioma is poorly defined. Here, we reported that TMEM97 was significantly increased in glioma tissues compared to non-tumorous brain tissues. Furthermore, TMEM97 levels were progressively increased with increasing histologic tumor grade in glioma. Higher TMEM97 expression level was correlated with shorter survival time of patients with glioma. Downregulation of TMEM97 through RNA interference inhibited cell proliferation and G1/S transition in two glioma cell lines, U87 and U373. More importantly, TMEM97 silencing induced a significant decrease in the expression of G1/S transition key regulators, cyclin D1, cyclin E, CDK2, and CDK4. Additionally, downregulation of TMEM97 in glioma cells notably repressed cell migration and cell invasion. Further analysis suggested that the decreased invasion was associated with alterations in EMT markers, including E-cadherin, β-catenin, and Twist. Since expression of TMEM97 seems to be associated with the oncogenic potential of glioma, and suppression of its expression can inhibit cancer cell growth and metastasis, TMEM97 may be a potential therapeutic target in human glioma.

摘要

神经胶质瘤是成人中枢神经系统中最常见的原发性脑肿瘤形式。最近有报道称跨膜蛋白97(TMEM97)在不同类型的人类肿瘤中表达改变且具有预后价值。然而,TMEM97与神经胶质瘤的关联尚不清楚。在此,我们报道与非肿瘤性脑组织相比,TMEM97在神经胶质瘤组织中显著增加。此外,在神经胶质瘤中,TMEM97水平随着组织学肿瘤分级的增加而逐渐升高。较高的TMEM97表达水平与神经胶质瘤患者较短的生存时间相关。通过RNA干扰下调TMEM97可抑制两种神经胶质瘤细胞系U87和U373的细胞增殖和G1/S期转换。更重要的是,TMEM97沉默导致G1/S期转换关键调节因子细胞周期蛋白D1、细胞周期蛋白E、细胞周期蛋白依赖性激酶2(CDK2)和细胞周期蛋白依赖性激酶4(CDK4)的表达显著降低。此外,下调神经胶质瘤细胞中的TMEM97可显著抑制细胞迁移和侵袭。进一步分析表明,侵袭减少与上皮-间质转化(EMT)标志物的改变有关,包括E-钙黏蛋白、β-连环蛋白和Twist。由于TMEM97的表达似乎与神经胶质瘤的致癌潜力相关,并且抑制其表达可抑制癌细胞生长和转移,因此TMEM97可能是人类神经胶质瘤的潜在治疗靶点。

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