Sogut Melis Savasan, Venugopal Chitra, Kandemir Basak, Dag Ugur, Mahendram Sujeivan, Singh Sheila, Gulfidan Gizem, Arga Kazim Yalcin, Yilmaz Bayram, Kurnaz Isil Aksan
Institute of Biotechnology, Gebze Technical University, 41400 Kocaeli, Turkey.
Molecular Neurobiology Laboratory (AxanLab), Department of Molecular Biology and Genetics, Gebze Technical University, 41400 Kocaeli, Turkey.
J Pers Med. 2021 Feb 14;11(2):125. doi: 10.3390/jpm11020125.
Elk-1, a member of the ternary complex factors (TCFs) within the ETS (E26 transformation-specific) domain superfamily, is a transcription factor implicated in neuroprotection, neurodegeneration, and brain tumor proliferation. Except for known targets, and , few targets of Elk-1 have been identified. Interestingly, , , and promoters were shown to be regulated by Elk-1. On the other hand, Elk-1 was shown to regulate the CD133 gene, which is highly expressed in brain-tumor-initiating cells (BTICs) and used as a marker for separating this cancer stem cell population. In this study, we have carried out microarray analysis in SH-SY5Y cells overexpressing Elk-1-VP16, which has revealed a large number of genes significantly regulated by Elk-1 that function in nervous system development, embryonic development, pluripotency, apoptosis, survival, and proliferation. Among these, we have shown that genes related to pluripotency, such as , , and , were indeed regulated by Elk-1, and in the context of brain tumors, we further showed that Elk-1 overexpression in CD133+ BTIC population results in the upregulation of these genes. When Elk-1 expression is silenced, the expression of these stemness genes is decreased. We propose that Elk-1 is a transcription factor upstream of these genes, regulating the self-renewal of CD133+ BTICs.
Elk-1是ETS（E26转化特异性）结构域超家族中三元复合因子（TCFs）的成员之一，是一种与神经保护、神经退行性变和脑肿瘤增殖有关的转录因子。除了已知的靶点和 外，Elk-1的靶点鲜有被鉴定出来的。有趣的是， 、 和 的启动子已被证明受Elk-1调控。另一方面，Elk-1被证明可调控CD133基因，该基因在脑肿瘤起始细胞（BTICs）中高表达，并用作分离这种癌症干细胞群体的标志物。在本研究中，我们对过表达Elk-1-VP16的SH-SY5Y细胞进行了微阵列分析，结果揭示了大量受Elk-1显著调控的基因，这些基因在神经系统发育、胚胎发育、多能性、细胞凋亡、存活和增殖中发挥作用。其中，我们已证明与多能性相关的基因，如 、 和 ，确实受Elk-1调控，并且在脑肿瘤的背景下，我们进一步表明在CD133+ BTIC群体中过表达Elk-1会导致这些基因的上调。当Elk-1表达沉默时，这些干性基因的表达会降低。我们提出Elk-1是这些基因上游的转录因子，调控CD133+ BTICs的自我更新。
