Shen Zhi-Gang, Liu Xiao-Zhou, Chen Chang-Xiu, Lu Jing-Min
Oncol Res. 2017 Nov 2;25(9):1555-1566. doi: 10.3727/096504017X14897158009178. Epub 2017 Mar 23.
E2F3a, as a member of the E2F family, is essential for cell division associated with the progression of many cancers. However, the biological effect of E2F3a on glioma is not understood as well. To investigate the functional mechanism of E2F3a in glioma, we examined the expression of E2F3a in glioma tissue and cell lines. We found that E2F3a was upregulated in glioma tissue compared with adjacent tissue, and this was associated with a poor survival rate. E2F3a was highly expressed in glioma cell lines compared with normal HEB cell lines. Knockdown of E2F3a significantly inhibited cell proliferation, promoted G0/G1 phase arrest, elevated apoptosis rates, and suppressed cell migration and invasion. However, overexpression of E2F3a markedly promoted cell proliferation, migration, and invasion and inhibited apoptosis. Moreover, in vivo studies showed that knockdown of E2F3a expression dramatically inhibited U373 tumor growth in a nude mouse model. Results of real-time PCR and Western blot showed that the depletion of E2F3a upregulated the expression levels of cell apoptosis-related proteins and downregulated migration-related proteins. Conversely, E2F3a overexpression downregulated the expression levels of cell apoptosis-related proteins and upregulated migration-related proteins. In conclusion, our results highlight the importance of E2F3a in glioma and provide new insights into the diagnostics and therapeutics of gliomas.
E2F3a作为E2F家族的一员，对于与多种癌症进展相关的细胞分裂至关重要。然而，E2F3a对胶质瘤的生物学作用尚未完全明确。为了研究E2F3a在胶质瘤中的功能机制，我们检测了E2F3a在胶质瘤组织和细胞系中的表达。我们发现，与相邻组织相比，E2F3a在胶质瘤组织中表达上调，且这与较差的生存率相关。与正常HEB细胞系相比，E2F3a在胶质瘤细胞系中高表达。敲低E2F3a可显著抑制细胞增殖，促进G0/G1期阻滞，提高凋亡率，并抑制细胞迁移和侵袭。然而，E2F3a的过表达显著促进细胞增殖、迁移和侵袭，并抑制凋亡。此外，体内研究表明，在裸鼠模型中敲低E2F3a表达可显著抑制U373肿瘤生长。实时PCR和蛋白质印迹结果显示，E2F3a的缺失上调了细胞凋亡相关蛋白的表达水平，下调了迁移相关蛋白的表达水平。相反，E2F3a的过表达下调了细胞凋亡相关蛋白的表达水平，上调了迁移相关蛋白的表达水平。总之，我们的结果突出了E2F3a在胶质瘤中的重要性，并为胶质瘤的诊断和治疗提供了新的见解。
