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Open AccessArticle

Decreased Expression of ZNF554 in Gliomas is Associated with the Activation of Tumor Pathways and Shorter Patient Survival

1
Systems Biology of Reproduction Research Group, Institute of Enzymology, Research Centre for Natural Sciences, H-1117 Budapest, Hungary
2
First Department of Pathology and Experimental Cancer Research, Semmelweis University, H-1085 Budapest, Hungary
3
Laboratory of Functional Genomics, Department of Genetics, Biological Research Centre, H-6726 Szeged, Hungary
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Department of Immunology, Eotvos Lorand University, H-1117 Budapest, Hungary
5
Maternity Private Clinic, H-1126 Budapest, Hungary
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Department of Obstetrics and Gynecology, Semmelweis University, H-1088 Budapest, Hungary
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Department of Pediatrics, Neurology, Neurosurgery, Wayne State University School of Medicine, Detroit, MI 48201, USA
8
Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(16), 5762; https://doi.org/10.3390/ijms21165762
Received: 23 June 2020 / Revised: 31 July 2020 / Accepted: 5 August 2020 / Published: 11 August 2020
(This article belongs to the Special Issue Molecular Biology of Brain Tumors)
Zinc finger protein 554 (ZNF554), a member of the Krüppel-associated box domain zinc finger protein subfamily, is predominantly expressed in the brain and placenta in humans. Recently, we unveiled that ZNF554 regulates trophoblast invasion during placentation and its decreased expression leads to the early pathogenesis of preeclampsia. Since ZNF proteins are immensely implicated in the development of several tumors including malignant tumors of the brain, here we explored the pathological role of ZNF554 in gliomas. We examined the expression of ZNF554 at mRNA and protein levels in normal brain and gliomas, and then we searched for genome-wide transcriptomic changes in U87 glioblastoma cells transiently overexpressing ZNF554. Immunohistochemistry of brain tissues in our cohort (n = 62) and analysis of large TCGA RNA-Seq data (n = 687) of control, oligodendroglioma, and astrocytoma tissues both revealed decreased expression of ZNF554 towards higher glioma grades. Furthermore, low ZNF554 expression was associated with shorter survival of grade III and IV astrocytoma patients. Overexpression of ZNF554 in U87 cells resulted in differential expression, mostly downregulation of 899 genes. The “PI3K-Akt signaling pathway”, known to be activated during glioma development, was the most impacted among 116 dysregulated pathways. Most affected pathways were cancer-related and/or immune-related. Congruently, cell proliferation was decreased and cell cycle was arrested in ZNF554-transfected glioma cells. These data collectively suggest that ZNF554 is a potential tumor suppressor and its decreased expression may lead to the loss of oncogene suppression, activation of tumor pathways, and shorter survival of patients with malignant glioma. View Full-Text
Keywords: glioma; glioblastoma; survival; transcriptome; zinc finger protein glioma; glioblastoma; survival; transcriptome; zinc finger protein
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Balogh, A.; Reiniger, L.; Hetey, S.; Kiraly, P.; Toth, E.; Karaszi, K.; Juhasz, K.; Gelencser, Z.; Zvara, A.; Szilagyi, A.; Puskas, L.G.; Matko, J.; Papp, Z.; Kovalszky, I.; Juhasz, C.; Than, N.G. Decreased Expression of ZNF554 in Gliomas is Associated with the Activation of Tumor Pathways and Shorter Patient Survival. Int. J. Mol. Sci. 2020, 21, 5762.

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