Choline Kinase Alpha Promoted Glioma Development by Activating PI3K/AKT Signaling Pathway

Cancer Biother Radiopharm. 2021 Nov 16. doi: 10.1089/cbr.2021.0294. Online ahead of print.

Abstract

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 of CHKA involved remains unclear. Therefore, this study aims to explore the mechanism of CHKA in glioma development. Methods: Immunohistochemistry, qRT-PCR, and Western blot were used to detect the expression of CHKA. 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 by CHKA. The enrichment analysis of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) helped to detect the signaling pathways CHKA affected. Tumor-bearing mice were established and evaluated by TUNEL assay, Ki-67 immunohistochemistry. and hematoxylin and eosin staining. Results: CHKA increased in glioma tissues and promoted cell proliferation, invasion, and migration, while inhibiting the glioma cell apoptosis. It was also showed that CHKA promoted glioma development in vivo. GO and KEGG analysis indicated that PI3K/AKT was significantly enriched in CHKA knockdown U251 cells. And CHKA promoted glioma development by activating PI3K/AKT signaling pathway. Conclusions: The authors demonstrated that CHKA was significantly elevated in glioma tissues. Mechanism analysis indicated that CHKA could promote glioma development by activating PI3K/AKT signaling pathway, suggesting that CHKA is promising to be a biomarker and therapeutic strategy for prognostic prediction of patients with glioma.

Keywords: CHKA; PI3K/AKT signaling; glioma.