Knockdown of DNA polymerase ζ relieved the chemoresistance of glioma via inhibiting the PI3K/AKT signaling pathway

ABSTRACT

Previous reports suggest that DNA polymerase ζ is highly expressed in glioma tissues. The present study aimed to investigate the roles of the REV7 subunit of DNA polymerase ζ in glioma cell chemoresistance and its underlying mechanisms. The bioinformatics method was used to compare the expression of REV7 in glioma and normal tissues. The expression of REV7 in glioma tumor samples and the adjacent tissue was examined by reverse transcription polymerase chain reaction. Moreover, an in vitro analysis using glioma cells was used to test the effects of REV7 siRNA on the proliferation and apoptosis of glioma cell line U251 cells, and the effect of REV7 siRNA on the sensitivity of the U251 cells to cisplatin was also explored. The expression of REV7 in glioma tumors was significantly increased. Moreover, the knockdown of REV7 in glioma cells decreased the proliferation and increased the apoptosis of U251 cells; moreover, REV7 siRNA also increased the sensitivity of U251 cells to cisplatin. Finally, REV7 may regulate the proliferation, apoptosis, and chemosensitivity of U251 cells by affecting phosphoinositide 3-kinase signaling. Our data suggest that REV7 is involved in the chemosensitivity of glioma cells and provides a theoretical basis for targeting DNA polymerase ζ to improve the sensitivity of glioma cells to chemotherapy.

Graphical Abstract

KEYWORDS:

• DNA polymerase ζ
• glioma
• REV7
• chemoresistance

Highlights

• REV7 is significantly higher in glioma tissues than surrounding tissues

• REV7 knockdown in glioma tissues decreased cell proliferation and increased apoptosis

• REV7 siRNA increased glioma chemosensitivity to cisplatin

REV7 regulates glioma proliferation, apoptosis, and chemosensitivity by PI3K pathway.

Disclosure statement

No potential conflict of interest was reported by the author(s).