Department of Neurosurgery, The Affiliated Huai'an Hospital of Xuzhou Medical University, The Second People's Hospital of Huai'an, Huai'an, 223002, China.
Department of Neurosurgery, Xinyi People's Hospital, Xuzhou, 221400, China.
Metab Brain Dis. 2022 Feb;37(2):489-499. doi: 10.1007/s11011-021-00863-9. Epub 2021 Nov 18.
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.
KIAA0101 是一种增殖细胞核抗原（PCNA）相关因子，据报道在几种人类恶性肿瘤中过表达，并被鉴定为癌基因。本研究旨在确定 KIAA0101 在胶质瘤进展中的功能和可能的机制。通过 GSE50161 和 GEPIA 数据集分析胶质瘤患者的 KIAA0101 表达。采用 Kaplan-Meier 生存分析评估生存分布。通过 qRT-PCR 和 Western blot 分析检测胶质瘤细胞中 KIAA0101 的表达。通过 MTT、流式细胞术、caspase-3 活性和 Transwell 测定研究 KIAA0101 的功能。此外，通过测量细胞外酸化率（ECAR）、葡萄糖消耗、乳酸生成和三磷酸腺苷（ATP）水平来确定糖酵解通量。通过 Western blot 分析检测磷酸肌醇-3-激酶（PI3K）/蛋白激酶 B（AKT）/哺乳动物雷帕霉素靶蛋白（mTOR）通路的变化。结果表明，KIAA0101 在胶质瘤组织和细胞中上调。高 KIAA0101 表达预示着胶质瘤患者预后不良。KIAA0101 耗竭抑制了胶质瘤细胞的增殖、迁移和侵袭，并触发了细胞凋亡。KIAA0101 沉默降低了胶质瘤细胞的 ECAR、葡萄糖消耗、乳酸生成和 ATP 水平，表明 KIAA0101 敲低抑制了胶质瘤细胞的糖酵解。机制上，KIAA0101 沉默通过抑制 PI3K/AKT/mTOR 通路抑制了胶质瘤的进展和糖酵解。总之，KIAA0101 沉默通过抑制 PI3K/AKT/mTOR 通路抑制了胶质瘤的进展和糖酵解。
