Ren Mingliang, Zhou Chun, Liang Hong, Wang Xuhui, Xu Lunshan
Department of Neurosurgery, Research Institute of Field Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.
Chem Biol Drug Des. 2015 Oct;86(4):715-22. doi: 10.1111/cbdd.12542. Epub 2015 Jul 28.
As the most common primary malignant brain tumors, gliomas cause more years of life lost than do any other tumors. Recently, abnormalities of the eukaryotic initiation factors (EIFs) have been reported in gliomas. Yet the role of EIF3D, which encodes a subunit of EIF3 multiprotein complex, remains poorly understood. In this study, we found EIF3D expression was positively correlated with WHO grades of gliomas. Furthermore, we employ lentivirus-mediated RNA interference (RNAi) to examine the physiological role of EIF3D in glioma cells. Decreased EIF3D expression in U251 and U87MG glioma cells caused a delay in cell growth and a disruption in colony formation. In addition, EIF3D knockdown induced G0/G1 phase cell cycle arrest and apoptosis. Cells with suppressed expression of EIF3D had a lower capacity to migrate in the transwell assay. These results suggest that EIF3D plays an important role in glioma development and may serve as a potential therapeutic target for human glioma.
作为最常见的原发性恶性脑肿瘤,胶质瘤比其他任何肿瘤导致更多的生命年损失。最近,在胶质瘤中已报道真核起始因子(EIFs)异常。然而,编码EIF3多蛋白复合体一个亚基的EIF3D的作用仍知之甚少。在本研究中,我们发现EIF3D表达与胶质瘤的世界卫生组织(WHO)分级呈正相关。此外,我们采用慢病毒介导的RNA干扰(RNAi)来研究EIF3D在胶质瘤细胞中的生理作用。U251和U87MG胶质瘤细胞中EIF3D表达降低导致细胞生长延迟和集落形成破坏。此外,EIF3D敲低诱导G0/G1期细胞周期停滞和凋亡。在transwell实验中,EIF3D表达受抑制的细胞迁移能力较低。这些结果表明,EIF3D在胶质瘤发展中起重要作用,可能作为人类胶质瘤的潜在治疗靶点。