DNA polymerase ζ suppresses the radiosensitivity of glioma cells by regulating the PI3K/AKT/mTOR pathway

Abstract

Glioblastoma is the most common glioma with high mortality and poor prognosis. Radiation resistance is one of the large challenges in the treatment of glioma. The study aimed to identify whether DNA polymerase ζ affects glioma cell radiosensitivity. The mRNA and protein levels of REV3L and REV7 were examined using quantitative real-time PCR and western blot. After REV3L and REV7 knockdown in a GBM cell line (A172), we assessed cell viability, colonies, apoptosis, and immune escape. The underlying mechanisms were evaluated using western blot and were confirmed using rescue experiments. The results showed that REV3L and REV7 levels were increased in glioma and related to poor survival. γ-ray treatment inhibited cell viability, survival fraction, and immune escape, and induced apoptosis of glioma cells from a GBM cell line, whereas knockdown of REV3L or REV7 enhanced these effects. Mechanically, silencing of REV3L or REV7 inactivated the PI3K/AKT/mTOR pathway. IGF-1 treatment abrogated the effects on cell viability, colonies, and apoptosis induced by REV3L or REV7 knocking down. Taken together, silencing of REV3L and REV7 inhibited radiation resistance via inactivating the PI3K/AKT/mTOR pathway, suggesting that targeting DNA polymerase ζ may be a new strategy to reduce the radiotherapy resistance of glioma.

Keywords:

• Glioma
• REV3L
• REV7
• radiosensitivity
• PI3K/AKT/mTOR pathway

Acknowledgments

Not applicable.

Ethical approval

This work was approved by the Ethics Committee of The First Affiliated Hospital of Jinan University (Approval No. 20221124). Informed contents were obtained from all subjects.

Authors’ contributions

All authors participated in the design, interpretation of the studies and analysis of the data, and review of the manuscript. JD drafted the work and revised it critically for important intellectual content; ZC, WD, and YX were responsible for the acquisition, analysis, or interpretation of data for the work; JY made substantial contributions to the conception or design of the work.

Disclosure statement

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

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

Not applicable.