Abstract
ObjectivesGlioma has a high degree of malignancy, strong invasiveness, and poor prognosis, which is always a serious threat to human health. Previous studies have reported that C2H2 zinc finger (ZNF) protein is involved in the progression of various cancers. In this study, the clinical significance, biological behavior, and molecule mechanism of ZNF655 in glioma were explored.MethodsThe expression of ZNF655 in glioma and its correlation with prognosis were analyzed through public datasets and immunohistochemical (IHC) staining. The shRNA-mediated ZNF655 knockdown was used to explore the effects of ZNF655 alteration on the phenotypes and tumorigenesis of human glioma cell lines. Chromatin immunoprecipitation (ChIP)-qPCR and luciferase reporter assays were performed to determine the potential mechanism of ZNF655 regulating Aurora kinase A (AURKA).ResultsZNF655 was abundantly expressed in glioma tissue and cell lines SHG-44 and U251. Knockdown of suppressed the progression of glioma cells, which was characterized by reduced proliferation, enhanced apoptosis, cycle repression in G2, inhibition of migration, and weakened tumorigenesis. Mechanistically, transcription factor ZNF655 activated the expression of AURKA by directly binding to the promoter of AURKA. In addition, downregulation of AURKA partially reversed the promoting effects of overexpression of ZNF655 on glioma cells.ConclusionsZNF655 promoted the progression of glioma by binding to the promoter of AURKA, which may be a promising target for molecular therapy.
Highlights
Glioma is the most common tumor of the human central nervous system, which is characterized by complex heterogeneity, high degree of malignancy, strong invasiveness, and poor prognosis [1, 2]
According to the database, we further found that Zinc-finger protein 655 (ZNF655) expression was positively correlated with overall survival (Figure 1B)
The results based on the Cancer Genome Atlas (TCGA) database further showed that the expression level of ZNF655 in glioblastoma (n = 155) was significantly higher than that of normal tissues (n = 5) (Figure 1C)
Summary
Glioma is the most common tumor of the human central nervous system, which is characterized by complex heterogeneity, high degree of malignancy, strong invasiveness, and poor prognosis [1, 2]. Gliomas are mainly composed of several subtypes, such as astrocytoma, oligodendroglioma, ependymoma, and neuroglioma hybrids [3, 4]. ZNF655 Promotes Glioma Through AURKA classified into grades I to grade IV according to the degree of malignancy [5]. Traditional therapies include a combination of surgery, radiation, and chemotherapy [6, 7]. Despite improved treatment outcomes in glioma patients, the median survival time is still only 12–18 months [8]. The solution of glioma as a challenging disease requires continuous exploration in the field of molecular biology to determine effective molecular therapy targets
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