Decreased expression of znf554 in gliomas is associated with the activation of tumor pathways and shorter patient survival

Andrea Balogh, Lilla Reiniger, Szabolcs Hetey, Peter Kiraly, Eszter Toth, Katalin Karaszi, Kata Juhasz, Zsolt Gelencser, Agnes Zvara, Andras Szilagyi, Laszlo G. Puskas, Janos Matko, Zoltan Papp, Ilona Kovalszky, Csaba Juhasz, Nandor Gabor Than

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number5762
Pages (from-to)1-18
Number of pages18
JournalInternational journal of molecular sciences
Volume21
Issue number16
DOIs
Publication statusPublished - Aug 2 2020

Keywords

  • Glioblastoma
  • Glioma
  • Survival
  • Transcriptome
  • Zinc finger protein

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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