Decreased Expression of ZNF554 in Gliomas is Associated with the Activation of Tumor Pathways and Shorter Patient Survival
| Autor: | László G. Puskás, Nandor Gabor Than, Andrea Balogh, János Matkó, András Szilágyi, Zoltán Papp, Péter Király, Csaba Juhász, Eszter Tóth, Kata Juhasz, Katalin Karaszi, Ilona Kovalszky, Szabolcs Hetey, Ágnes Zvara, Lilla Reiniger, Zsolt Gelencser |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
lcsh:Chemistry lcsh:QH301-705.5 Spectroscopy Zinc finger Brain Neoplasms Astrocytoma General Medicine Glioma Cell cycle Middle Aged Computer Science Applications Gene Expression Regulation Neoplastic medicine.anatomical_structure Female Signal transduction Signal Transduction Adult zinc finger protein Adolescent Kruppel-Like Transcription Factors Biology survival Catalysis Article Inorganic Chemistry Young Adult Cell Line Tumor medicine Humans RNA Messenger Physical and Theoretical Chemistry Molecular Biology neoplasms Aged Cell Proliferation Oncogene Genome Human Organic Chemistry glioblastoma Trophoblast Cell Cycle Checkpoints medicine.disease Survival Analysis nervous system diseases body regions lcsh:Biology (General) lcsh:QD1-999 Cancer research Oligodendroglioma transcriptome |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 21, Iss 5762, p 5762 (2020) Volume 21 Issue 16 |
| ISSN: | 1422-0067 |
| Popis: | Zinc finger protein 554 (ZNF554), a member of the Krü ppel-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 &ldquo PI3K-Akt signaling pathway&rdquo 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. |
| Databáze: | OpenAIRE |
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