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.
