Host: The Japanese Society of Toxicology
Name : The 50th Annual Meeting of the Japanese Society of Toxicology
Date : June 19, 2023 - June 21, 2023
Glioblastoma (GBM) is an intractable brain tumor, and the development of new therapeutic strategies is needed. Based on in silico analysis of gene expression in GBM patient tissues, we found that patients with high selenoprotein P (SeP) expression have a worse prognosis. Interestingly, high expression of CCDC152, a gene encoded by the antisense strand of the SeP gene, correlated with higher-grade GBM. Therefore, we aimed to elucidate the mechanism by which this locus is involved in the malignant phenotype of brain tumors. Our analysis indicated that Glioblastoma cell line T98G cells express both SeP and CCDC152 genes. Transfection of the cells with siRNAs for SeP or CCDC152 resulted in the inhibition of cell growth. SeP is thought to exhibit its cell growth effects via its receptor ApoER2. ApoER2 siRNA reduced cell proliferation, and no additive effects were observed with dual suppression of SeP and ApoER2 expressions, suggesting that SeP/ApoER2 exert their cell proliferative effects through the same pathway. In addition, RNA-seq analysis of ApoER2-deficient T98G cells suggests that the suppression of ApoER2 expression caused significant changes in cell cycle-related genes, and the cell division cycle of ApoER2-deficient T98G cells is arrested in the M phase. SeP and CCDC152 may be involved in the promotion of GBM proliferation, at least through ApoER2-mediated enhancement of cell division. ApoER2 is also known to be involved in the resistance to anti-cancer drug-induced ferroptosis via enhancement of selenium uptake. Suppression of CCDC152 expression enhanced ferroptosis suggests that the above mechanism is also involved in the acquisition of anti-cancer drug resistance.
