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Volume 11
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Article

ETS-Domain Transcription Factor Elk-1 Regulates Stemness Genes in Brain Tumors and CD133+ BrainTumor-Initiating Cells

by
Melis Savasan Sogut
1,2,3,
Chitra Venugopal
4,
Basak Kandemir
1,2,3,†,
Ugur Dag
3,‡,
Sujeivan Mahendram
4,
Sheila Singh
4,
Gizem Gulfidan
5,
Kazim Yalcin Arga
5,
Bayram Yilmaz
6,* and
Isil Aksan Kurnaz
1,2,*
1
Institute of Biotechnology, Gebze Technical University, 41400 Kocaeli, Turkey
2
Molecular Neurobiology Laboratory (AxanLab), Department of Molecular Biology and Genetics, Gebze Technical University, 41400 Kocaeli, Turkey
3
Biotechnology Graduate Program, Graduate School of Sciences, Yeditepe University, 26 Agustos Yerlesimi, Kayisdagi, 34755 Istanbul, Turkey
4
Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8S 4K1, Canada
5
Department of Bioengineering, Marmara University, 34722 Istanbul, Turkey
6
Department of Physiology, Faculty of Medicine, Yeditepe University, 26 Agustos Yerlesimi, Kayisdagi, 34755 Istanbul, Turkey
*
Authors to whom correspondence should be addressed.
†
Present address: Department of Molecular Biology and Genetics, Baskent University, 06790 Ankara, Turkey.
‡
Present address: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139-4307, USA.
J. Pers. Med. 2021, 11(2), 125; https://doi.org/10.3390/jpm11020125
Submission received: 20 January 2021 / Revised: 4 February 2021 / Accepted: 9 February 2021 / Published: 14 February 2021
(This article belongs to the Special Issue Recent Developments in Cancer Systems Biology)
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Abstract

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, c-fos and egr-1, few targets of Elk-1 have been identified. Interestingly, SMN, SOD1, and PSEN1 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 Sox2, Nanog, and Oct4, 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.
Keywords: ETS; Elk-1; stem cell; microarray; brain-tumor-initiating cell (BTIC) ETS; Elk-1; stem cell; microarray; brain-tumor-initiating cell (BTIC)

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MDPI and ACS Style

Sogut, M.S.; Venugopal, C.; Kandemir, B.; Dag, U.; Mahendram, S.; Singh, S.; Gulfidan, G.; Arga, K.Y.; Yilmaz, B.; Kurnaz, I.A. ETS-Domain Transcription Factor Elk-1 Regulates Stemness Genes in Brain Tumors and CD133+ BrainTumor-Initiating Cells. J. Pers. Med. 2021, 11, 125. https://doi.org/10.3390/jpm11020125

AMA Style

Sogut MS, Venugopal C, Kandemir B, Dag U, Mahendram S, Singh S, Gulfidan G, Arga KY, Yilmaz B, Kurnaz IA. ETS-Domain Transcription Factor Elk-1 Regulates Stemness Genes in Brain Tumors and CD133+ BrainTumor-Initiating Cells. Journal of Personalized Medicine. 2021; 11(2):125. https://doi.org/10.3390/jpm11020125

Chicago/Turabian Style

Sogut, Melis Savasan, Chitra Venugopal, Basak Kandemir, Ugur Dag, Sujeivan Mahendram, Sheila Singh, Gizem Gulfidan, Kazim Yalcin Arga, Bayram Yilmaz, and Isil Aksan Kurnaz. 2021. "ETS-Domain Transcription Factor Elk-1 Regulates Stemness Genes in Brain Tumors and CD133+ BrainTumor-Initiating Cells" Journal of Personalized Medicine 11, no. 2: 125. https://doi.org/10.3390/jpm11020125

APA Style

Sogut, M. S., Venugopal, C., Kandemir, B., Dag, U., Mahendram, S., Singh, S., Gulfidan, G., Arga, K. Y., Yilmaz, B., & Kurnaz, I. A. (2021). ETS-Domain Transcription Factor Elk-1 Regulates Stemness Genes in Brain Tumors and CD133+ BrainTumor-Initiating Cells. Journal of Personalized Medicine, 11(2), 125. https://doi.org/10.3390/jpm11020125

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