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

IF 3.3 4区医学 Q3 IMMUNOLOGY

Autoimmunity Pub Date : 2023-12-01 DOI:10.1080/08916934.2023.2234101

Jiqiang Ding, Zhisheng Chen, Weilong Ding, Yongsheng Xiang, Junbao Yang

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引用次数: 0

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.

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DNA聚合酶ζ通过调节PI3K/AKT/mTOR通路抑制胶质瘤细胞的放射敏感性。

胶质母细胞瘤是最常见的胶质瘤，死亡率高，预后差。抗辐射是治疗胶质瘤的一大挑战。该研究旨在确定DNA聚合酶ζ是否影响神经胶质瘤细胞的放射敏感性。使用实时定量PCR和蛋白质印迹检测REV3L和REV7的mRNA和蛋白质水平。在GBM细胞系（A172）中敲低REV3L和REV7后，我们评估了细胞活力、集落、凋亡和免疫逃逸。使用蛋白质印迹评估潜在的机制，并使用拯救实验证实。结果显示，胶质瘤中REV3L和REV7水平升高，与生存率低有关。γ射线治疗抑制了GBM细胞系的细胞活力、存活率和免疫逃逸，并诱导了胶质瘤细胞的凋亡，而敲低REV3L或REV7增强了这些作用。在机制上，REV3L或REV7的沉默使PI3K/AKT/mTOR途径失活。IGF-1治疗消除了REV3L或REV7敲除诱导的细胞活力、集落和凋亡的影响。总之，REV3L和REV7的沉默通过使PI3K/AKT/mTOR通路失活来抑制放疗耐药性，这表明靶向DNA聚合酶ζ可能是降低神经胶质瘤放疗耐药性的一种新策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Autoimmunity 医学-免疫学

CiteScore

5.70

自引率

8.60%

发文量

审稿时长

6-12 weeks

期刊介绍： Autoimmunity is an international, peer reviewed journal that publishes articles on cell and molecular immunology, immunogenetics, molecular biology and autoimmunity. Current understanding of immunity and autoimmunity is being furthered by the progress in new molecular sciences that has recently been little short of spectacular. In addition to the basic elements and mechanisms of the immune system, Autoimmunity is interested in the cellular and molecular processes associated with systemic lupus erythematosus, rheumatoid arthritis, Sjogren syndrome, type I diabetes, multiple sclerosis and other systemic and organ-specific autoimmune disorders. The journal reflects the immunology areas where scientific progress is most rapid. It is a valuable tool to basic and translational researchers in cell biology, genetics and molecular biology of immunity and autoimmunity.