Choline Kinase Alpha Promoted Glioma Development by Activating PI3K/AKT Signaling Pathway
Choline Kinase Alpha Promoted Glioma Development by Activating PI3K/AKT Signaling Pathway
复制标题
胆碱激酶 Alpha 通过激活 PI3K/AKT 信号通路促进神经胶质瘤的发展
DOI：
10.1089/cbr.2021.0294
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发表时间：
2021
影响因子：
3.4
通讯作者：
Hui Ma
中科院分区：
文献类型：
--
作者：
Yourui Zou;Ling Huang;Shengyu Sun;Fangqian Yue;Zhuoqi Li;Yue Ma;Hui Ma
目的：最常见的成人原发性脑肿瘤是神经胶质瘤。胆碱激酶α（CHKA）已被证明在神经胶质瘤中发挥重要作用。然而，CHKA参与的机制仍不清楚。因此，本研究旨在探讨CHKA在胶质瘤发生发展中的作用机制。方法：采用免疫组化、qRT-PCR、Western blot等方法检测CHKA的表达。进行流式细胞术、细胞计数试剂盒-8 (CCK-8)、Transwell 和伤口愈合测定，分别评估细胞凋亡、增殖、侵袭和迁移。 RNA测序用于探索受CHKA影响的差异表达基因。基因本体（GO）和京都基因与基因组百科全书（KEGG）的富集分析有助于检测CHKA影响的信号通路。建立荷瘤小鼠并通过TUNEL测定、Ki-67免疫组织化学进行评估。结果：胶质瘤组织中CHKA升高，促进细胞增殖、侵袭、迁移，同时抑制胶质瘤细胞凋亡。 GO和KEGG分析表明，CHKA敲低的U251细胞中PI3K/AKT显着富集。并且CHKA通过激活PI3K/AKT信号通路促进胶质瘤的发展。结论：作者证明CHKA在胶质瘤组织中显着升高。机制分析表明CHKA可通过激活PI3K/AKT信号通路促进胶质瘤的发生发展，提示CHKA有望成为胶质瘤患者预后预测的生物标志物和治疗策略。
Objective:The most commonly reported primary brain tumor in adults is glioma. Choline kinase alpha (CHKA) has been proved to play important roles in glioma. However, the mechanism ofCHKAinvolved remains unclear. Therefore, this study aims to explore the mechanism ofCHKAin glioma development.Methods:Immunohistochemistry, qRT-PCR, and Western blot were used to detect the expression ofCHKA. Flow cytometry, Cell Counting Kit-8 (CCK-8), transwell, and wound healing assays were performed to evaluate cell apoptosis, proliferation, invasion, and migration, respectively. RNA sequencing was used to explore the differentially expressed genes affected byCHKA. The enrichment analysis of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) helped to detect the signaling pathwaysCHKAaffected. Tumor-bearing mice were established and evaluated by TUNEL assay, Ki-67 immunohistochemistry. and hematoxylin and eosin staining.Results:CHKAincreased in glioma tissues and promoted cell proliferation, invasion, and migration, while inhibiting the glioma cell apoptosis. It was also showed thatCHKApromoted glioma developmentin vivo.GOand KEGG analysis indicated that PI3K/AKT was significantly enriched inCHKAknockdown U251 cells. AndCHKApromoted glioma development by activating PI3K/AKT signaling pathway.Conclusions:The authors demonstrated thatCHKAwas significantly elevated in glioma tissues. Mechanism analysis indicated thatCHKAcould promote glioma development by activating PI3K/AKT signaling pathway, suggesting thatCHKAis promising to be a biomarker and therapeutic strategy for prognostic prediction of patients with glioma.