Zheng K B, Xie J, Li Y T, Yuan Y, Wang Y, Li Ch, Shi Y F
Bratisl Lek Listy. 2019;120(4):309-315. doi: 10.4149/BLL_2019_049.
Glioma is a type of tumor that occurs in the brain and accounts for almost 30 % of all brain and central nervous system tumors and 80 % of all malignant brain tumors. In this study, we investigate the role of cAMP response element-binding protein (CREB) in the progression of glioma.
Tissue samples from glioma patients were collected and examined for expression of CREB and its correlation with tumor grades. CREB was then knocked down via siRNA to see if reduced expression of CREB affects cell proliferation and migration. Factors involved in cell cycles, adhesion and apoptosis were examined as well. Moreover, CRESP/CAS9 mediated knockout of CREB was conducted and athymic Nude mice model was used to investigate CREB's role in vivo.
The evaluated expression level of CREB in glioma patients was correlated with tumor grades. Knockdown of CREB via siRNA in glioma cell line U251 significantly inhibited the proliferation and migration of tumor cells. Moreover, CyclinD1 and Bcl-2 expression were reduced, as well as phosphorylation of IRK1/2 and AKT. Additionally, knockout of CREB via CRESP/CAS9 inhibited tumor formation of U251 cells in athymic Nude mice model.
In conclusion, our data suggest that over expression of CREB may contribute to progression of glioma and knockdown of CREB expression may serve as a novel target for therapy (Tab. 1, Fig. 6, Ref. 25).
胶质瘤是一种发生于脑部的肿瘤，占所有脑及中枢神经系统肿瘤的近30%，以及所有恶性脑肿瘤的80%。在本研究中，我们探究了环磷腺苷效应元件结合蛋白（CREB）在胶质瘤进展中的作用。
收集胶质瘤患者的组织样本，检测CREB的表达及其与肿瘤分级的相关性。然后通过小干扰RNA（siRNA）敲低CREB，以观察CREB表达降低是否影响细胞增殖和迁移。同时检测细胞周期、黏附及凋亡相关因子。此外，进行了CRISPR/CAS9介导的CREB基因敲除，并利用无胸腺裸鼠模型研究CREB在体内的作用。
评估的胶质瘤患者中CREB的表达水平与肿瘤分级相关。在胶质瘤细胞系U251中通过siRNA敲低CREB可显著抑制肿瘤细胞的增殖和迁移。此外，细胞周期蛋白D1（CyclinD1）和Bcl-2的表达降低，以及胰岛素受体底物1/2（IRK1/2）和蛋白激酶B（AKT）的磷酸化水平降低。另外，通过CRISPR/CAS9敲除CREB可抑制U251细胞在无胸腺裸鼠模型中的肿瘤形成。
总之，我们的数据表明，CREB的过表达可能促进胶质瘤进展，而敲低CREB表达可能成为一种新的治疗靶点（表1，图6，参考文献25）。
