WDR34 affects PI3K/Akt and Wnt/ß-catenin pathways to regulates malignant biological behaviors of glioma cells.
J Neurooncol
; 156(2): 281-293, 2022 Jan.
Article
de En
| MEDLINE
| ID: mdl-34981299
ABSTRACT
PURPOSE:
Glioma is the most prevalent primary intracranial tumor globally. WDR34, a member of the WDR superfamily with five WD40 repeats, is involved in the pathogenesis of several tumors. However, the role of WDR34 in glioma progression is unknown.METHODS:
The expression and prognostic significance of WDR34 in glioma patients were analyzed using GEPIA. WDR34 expression was detected by qRT-PCR. Western blot was employed to determine the expression of Ki67, proliferating cell nuclear antigen (PCNA), matrix metallopeptidase (MMP)2, MMP9, phosphatase and tensin homolog, protein kinase B (Akt), phosphorylated Akt, ß-catenin, and c-Myc. CCK-8, BrdU incorporation assay, Transwell invasion assay, flow cytometry analysis, and measurement of caspase-3 and caspase-9 activities were conducted to examine the effects of WDR34 knockdown on glioma cells.RESULTS:
WDR34 was upregulated in glioma, which predicted a poor prognosis in glioma patients. WDR34 knockdown inhibited cell proliferation and reduced the expression of Ki67 and PCNA in glioma cells. WDR34 knockdown repressed the invasive ability of glioma cells by decreasing MMP-2 and MMP-9 expression. WDR34 knockdown increased the apoptotic rate and caspase-3 and caspase-9 activities in glioma cells. The PI3K/Akt and Wnt/ß-catenin pathways were inhibited after WDR34 knockdown in glioma cells. Moreover, overexpression of Akt or ß-catenin reversed the function of WDR34 knockdown on proliferation, invasion, and apoptosis. WDR34 knockdown reduced tumor growth in vivo.CONCLUSIONS:
WDR34 knockdown inhibited malignant biological behaviors of glioma cells by inactivating the PI3K/Akt and Wnt/ß-catenin signaling cascades.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Tumeurs du cerveau
/
Protéines de transport
/
Régulation de l'expression des gènes tumoraux
/
Gliome
Limites:
Humans
Langue:
En
Journal:
J Neurooncol
Année:
2022
Type de document:
Article