Balogh, Andrea and Reiniger, Lilla and Hetey, Szabolcs and Király, Péter and Tóth, Eszter and Karászi, Katalin and Juhász, Kata and Gelencsér, Zsolt and Zvara, Ágnes and Szilágyi, András and Puskás, László and Matkó, János and Papp, Zoltán and Kovalszky, Ilona and Juhász, Csaba and Than, Nándor Gábor (2020) Decreased Expression ofZNF554in Gliomas is Associated with the Activation of Tumor Pathways and Shorter Patient Survival. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 21 (16). ISSN 1661-6596
|
Text
ijms-21-05762-v4.pdf Download (2MB) | Preview |
Abstract
Zinc finger protein 554 (ZNF554), a member of the Kruppel-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 overexpressingZNF554. 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 ofZNF554towards higher glioma grades. Furthermore, lowZNF554expression was associated with shorter survival of grade III and IV astrocytoma patients. Overexpression ofZNF554in 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 inZNF554-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.
| Item Type: | Article |
|---|---|
| Additional Information: | Systems Biology of Reproduction Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, H-1117, Hungary First Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, H-1085, Hungary Laboratory of Functional Genomics, Department of Genetics, Biological Research Centre, Szeged, H-6726, Hungary Department of Immunology, Eotvos Lorand University, Budapest, H-1117, Hungary Maternity Private Clinic, Budapest, H-1126, Hungary Department of Obstetrics and Gynecology, Semmelweis University, Budapest, H-1088, Hungary Department of Pediatrics, Neurology, Neurosurgery, Wayne State University School of Medicine, Detroit, MI 48201, United States Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, United States Export Date: 22 September 2020 Correspondence Address: Than, N.G.; Systems Biology of Reproduction Research Group, Institute of Enzymology, Research Centre for Natural Sciences, First Department of Pathology and Experimental Cancer Research, Semmelweis University, Maternity Private ClinicHungary; email: than.gabor@ttk.hu Funding details: Hungarian Scientific Research Fund, OTKA, K128262 Funding text 1: Funding: This research was supported by the Hungarian Scientific Research Fund (K128262 grant to A.Sz. and K124862 grant to N.G.T.); Hungarian Academy of Sciences (Momentum LP2014-7/2014 grant to N.G.T., Premium_2019-436 grant to B.A., Young Research Fellowships to Sz.H. and E.T.), and Hungarian National Research, Development, and Innovation Office (FIEK_16-1-2016-0005 grant and VEKOP-2.3.3-15-2017-0014 grant to N.G.T.). Systems Biology of Reproduction Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, H-1117, Hungary First Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, H-1085, Hungary Laboratory of Functional Genomics, Department of Genetics, Biological Research Centre, Szeged, H-6726, Hungary Department of Immunology, Eotvos Lorand University, Budapest, H-1117, Hungary Maternity Private Clinic, Budapest, H-1126, Hungary Department of Obstetrics and Gynecology, Semmelweis University, Budapest, H-1088, Hungary Department of Pediatrics, Neurology, Neurosurgery, Wayne State University School of Medicine, Detroit, MI 48201, United States Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, United States Export Date: 19 October 2020 Correspondence Address: Than, N.G.; Systems Biology of Reproduction Research Group, Institute of Enzymology, Research Centre for Natural Sciences, First Department of Pathology and Experimental Cancer Research, Semmelweis University, Maternity Private ClinicHungary; email: than.gabor@ttk.hu Export Date: 22 November 2020 |
| Uncontrolled Keywords: | BRAIN; CELLS; DIFFERENTIATION; DOMAINS; FAMILY; GLIOMA; SURVIVAL; TRANSCRIPTION FACTORS; glioblastoma; Transcriptome; GENE-THERAPY; HUMAN GLIOBLASTOMA; Biochemistry & Molecular Biology; ZINC-FINGER PROTEINS; |
| Subjects: | Q Science / természettudomány > QH Natural history / természetrajz > QH426 Genetics / genetika, örökléstan |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 26 Nov 2020 13:21 |
| Last Modified: | 26 Nov 2020 13:21 |
| URI: | http://real.mtak.hu/id/eprint/117485 |
Actions (login required)
 |
Edit Item |
