Jiandong Zuo1, Chun Liu2, Hongzao Ni3, Zhengquan Yu4. 1. Department of Neurosurgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, People's Republic of China. 2. Department of Neurosurgery, Lianshui People's Hospital Affiliated to Kangda College of Nanjing Medical University, Huai'an, 210009, People's Republic of China. 3. Department of Neurosurgery, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an Second People's Hospital, Huai'an, 223002, People's Republic of China. 4. Department of Neurosurgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, People's Republic of China. yuzhengquan666888@163.com.
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, β-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/β-catenin pathways were inhibited after WDR34 knockdown in glioma cells. Moreover, overexpression of Akt or β-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/β-catenin signaling cascades.
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, β-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/β-catenin pathways were inhibited after WDR34 knockdown in glioma cells. Moreover, overexpression of Akt or β-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/β-catenin signaling cascades.