Tian Yuan, Hao Shaobo, Ye Minhua, Zhang Anling, Nan Yang, Wang Guangxiu, Jia Zhifan, Yu Kai, Guo Lianmei, Pu Peiyu, Huang Qiang, Zhong Yue
Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, People's Republic of China; Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052, People's Republic of China; Key Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government, People's Republic of China.
Department of Neurosurgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province 330006, People's Republic of China.
Biochem Biophys Res Commun. 2015 Mar 6;458(2):307-12. doi: 10.1016/j.bbrc.2015.01.105. Epub 2015 Feb 3.
We demonstrated that IKBKE is overexpressed in human gliomas and that the downregulation of IKBKE markedly inhibits the proliferative and invasive abilities of glioma cells, which is consistent with the results reported by several different research groups. Therefore, IKBKE represents a promising therapeutic target for the treatment of glioma. In the present study, we verified that the microRNAs let-7b and let-7i target IKBKE through luciferase assays and found that let-7b/i mimics can knock down IKBKE and upregulate E-cadherin through western blot analysis. Moreover, the expression levels of let-7b/i were significantly lower in glioma cell lines than that in normal brain tissues, as determined by quantitative real-time PCR. Furthermore, let-7b/i inhibit the invasion and migration of glioma cells, as determined through wound healing and Transwell assays. The above-mentioned data suggest that let-7b/i inhibit the invasive ability of glioma cells by directly downregulating IKBKE and indirectly upregulating E-cadherin.
我们证明IKBKE在人类胶质瘤中过表达,并且IKBKE的下调显著抑制胶质瘤细胞的增殖和侵袭能力,这与几个不同研究小组报道的结果一致。因此,IKBKE是治疗胶质瘤的一个有前景的治疗靶点。在本研究中,我们通过荧光素酶测定验证了微小RNA let-7b和let-7i靶向IKBKE,并通过蛋白质免疫印迹分析发现let-7b/i模拟物可以敲低IKBKE并上调E-钙黏蛋白。此外,通过定量实时PCR测定,胶质瘤细胞系中let-7b/i的表达水平显著低于正常脑组织。此外,通过伤口愈合和Transwell测定确定,let-7b/i抑制胶质瘤细胞的侵袭和迁移。上述数据表明,let-7b/i通过直接下调IKBKE和间接上调E-钙黏蛋白来抑制胶质瘤细胞的侵袭能力。