Department of Neurology, The First Hospital of Jilin University, Changchun 130021, P.R. China.
Department of Neurosurgery, The Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, P.R. China.
Int J Oncol. 2014 Mar;44(3):797-804. doi: 10.3892/ijo.2014.2247. Epub 2014 Jan 8.
The Kank1 gene is one of the important members of the Kank gene family. As an important adaptor protein, Kank1 plays a significant role in the genesis and development of many malignant tumors. It was recently discovered that the Kank1 gene is a new cancer suppressor, and its expression is significantly downregulated or it is not expressed in kidney cancer, bladder cancer, prostate cancer, lung cancer and breast cancer. However, no report on the role of Kank1 in the genesis of brain glioma is available to date. In this study, we found significantly lower expression of the Kank1 gene in human brain glioma cells compared to the other cells evaluated. We used RNA interference techniques to silence Kank1 gene expression and found acceleration of tumor cell proliferation. However, when the Kank1 gene was upregulated, cell apoptosis occurred and the cell cycle was blocked in the G0/G1 phase. Also, we found that upregulating the Kank1 gene may result in the change of mitochondrial membrane potential, and the regulation of Bax and Bcl-2 may promote the mitochondria to release cytochrome C so as to activate Caspase-9 and -3. Thus, the human brain glioma apoptosis induced by upregulation of the Kank1 gene is closely relevant to the mitochondrial pathway.
Kank1 基因是 Kank 基因家族的重要成员之一。作为一种重要的衔接蛋白，Kank1 在许多恶性肿瘤的发生和发展中起着重要作用。最近发现 Kank1 基因是一种新的抑癌基因，其在肾癌、膀胱癌、前列腺癌、肺癌和乳腺癌中的表达显著下调或不表达。然而，目前尚无关于 Kank1 在脑胶质瘤发生中的作用的报道。在本研究中，我们发现与其他评估的细胞相比，人脑胶质瘤细胞中 Kank1 基因的表达明显降低。我们使用 RNA 干扰技术沉默 Kank1 基因的表达，发现肿瘤细胞增殖加速。然而，当 Kank1 基因上调时，细胞发生凋亡，细胞周期被阻滞在 G0/G1 期。此外，我们发现上调 Kank1 基因可能导致线粒体膜电位的改变，Bax 和 Bcl-2 的调节可能促使线粒体释放细胞色素 C，从而激活 Caspase-9 和 -3。因此，上调 Kank1 基因诱导的人脑胶质瘤细胞凋亡与线粒体途径密切相关。
