4.5 Article

Zinc finger and SCAN domain-containing 18 suppresses the proliferation, self-renewal, and drug resistance of glioblastoma cells

Journal

HELIYON
Volume 9, Issue 6, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.heliyon.2023.e17000

Keywords

Zinc finger and SCAN domain-Containing 18; Glioblastoma; Drug sensitivity; Self-renewal; Glioma-associated oncogene homolog 1

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This study characterized the expression and function of ZSCAN18 in human glioblastoma cell lines. ZSCAN18 was significantly down-regulated in glioblastoma cell lines compared to normal astrocytes. Overexpression of ZSCAN18 suppressed glioblastoma cell proliferation, sphere formation, and the expression of SOX2 and OCT4.
Elucidation of cellular and molecular mechanisms key to glioblastoma growth, self-renewal, survival, and metastasis is important for developing novel therapeutic strategies. In this study, the expression and function of zinc finger and SCAN domain-containing 18 (ZSCAN18) in human glioblastoma cell lines were characterized. Compared with normal astrocytes, ZSCAN18 was significantly down-regulated in all tested glioblastoma cell lines, with the LN-229 cell line having the lowest ZSCAN18 expression. Lentivirus-mediated ZSCAN18 overexpression suppressed glio-blastoma cell proliferation, sphere formation, and SOX2 and OCT4 expression, implying the negative role of ZSCAN18 in glioblastoma development. ZSCAN18 overexpression enhanced the sensitivity of glioblastoma cells to Temozolomide. The glioblastoma implantation model showed a consistent inhibitory effect of ZSCAN18 on the proliferation and self-renewal of glioblastoma cells in vivo. Notably, ZSCAN18 overexpression resulted in the down-regulation of glioma-associated oncogene homolog 1 (GLI1) which is the terminal component of the Hedgehog signaling. Lentivirus-mediated GLI1 overexpression restored the proliferation and promoted the resistance of glioblastoma cells to Temozolomide. However, GLI1 overexpression did not affect the self-renewal of ZSCAN18-overexpressing glioblastoma cells. Taken together, this research uncovers the role of ZSCAN18 in regulating glioblastoma cell growth and maintenance. ZSCAN18 could be a potential glioblastoma biomarker.

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