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KIAA0101 knockdown inhibits glioma progression and glycolysis by inactivating the PI3K/AKT/mTOR pathway

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Abstract

KIAA0101, a proliferating cell nuclear antigen (PCNA)-associated factor, is reported to be overexpressed and identified as an oncogene in several human malignancies. The purpose of this study is to determine the function and possible mechanism of KIAA0101 in glioma progression. KIAA0101 expression in glioma patients was analyzed by GSE50161 and GEPIA datasets. Kaplan-Meier survival analysis was used to evaluate the survival distributions. KIAA0101 expression in glioma cells were detected by qRT-PCR and western blot analyses. The function of KIAA0101 was investigated using MTT, flow cytometry, caspase-3 activity, and Transwell assays. Additionally, glycolytic flux was determined by measuring extracellular acidification rate (ECAR), glucose consumption, lactate production, and adenosine triphosphate (ATP) level. The changes of phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway were detected by western blot analysis. Results showed that KIAA0101 was upregulated in glioma tissues and cells. High KIAA0101 expression predicted a poor prognosis in glioma patients. KIAA0101 depletion impeded cell proliferation, migration, and invasion and triggered apoptosis in glioma cells. KIAA0101 silencing reduced the ECAR, glucose consumption, lactate production, and ATP level in glioma cells, suggesting that KIAA0101 knockdown inhibited glycolysis in glioma cells. Mechanistically, KIAA0101 knockdown inhibited the PI3K/AKT/mTOR pathway. In conclusion, KIAA0101 silencing inhibited glioma progression and glycolysis by inactivating the PI3K/AKT/mTOR pathway.

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The data used to support the findings of this study are available from the corresponding author upon request.

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Authors and Affiliations

  1. Department of Neurosurgery, The Affiliated Huai’an Hospital of Xuzhou Medical University, The Second People’s Hospital of Huai’an, Huai’an, 223002, China

    Kai Wang

  2. Department of Neurosurgery, Xinyi People’s Hospital, Xuzhou, 221400, China

    Jinxiao Li

  3. Department of Neurosurgery, The Second Affiliated Hospital of Xuzhou Medical University, 32 Meijian Road, Xuzhou, 221006, China

    Botao Zhou

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  1. Kai Wang
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  2. Jinxiao Li
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Kai Wang and Jinxiao Li performed the experiments, analyzed the data, and wrote the paper. Botao Zhou designed and monitored this study.

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Correspondence to Botao Zhou.

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Kai Wang and Jinxiao Li are co-first authors.

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Wang, K., Li, J. & Zhou, B. KIAA0101 knockdown inhibits glioma progression and glycolysis by inactivating the PI3K/AKT/mTOR pathway. Metab Brain Dis 37, 489–499 (2022). https://doi.org/10.1007/s11011-021-00863-9

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  • DOI: https://doi.org/10.1007/s11011-021-00863-9

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