PRMT7 Inhibitor SGC3027 Enhances Radiotherapy Efficacy via Activating ATM Kinase in Non-Small Cell Lung Carcinoma.

IF 2.7 3区 医学 Q2 BIOLOGY Radiation research Pub Date : 2025-04-01 DOI:10.1667/RADE-24-00242.1
Ya Heng, Feifei Wang, Zhonghui Zhang, Zebang Lin, Dahai Zhao, Qiuling Li
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Abstract

Non-small-cell lung cancer (NSCLC) is the leading cause of tumor-related death in humans. Radiotherapy is a crucial strategy for NSCLC treatment, although its effectiveness is limited by the radio-resistance of tumor cells. Our current research finds that the protein arginine methyltransferase 7 (PRMT7) is upregulated in NSCLC and correlates with poor prognosis. Pharmacological inhibition of PRMT7 by SGC3027, a specific small-molecule PRMT7 inhibitor, suppresses the proliferation, migration and invasion of NSCLC. Combining irradiation with SGC3027 strengthens the impact of irradiation on the biological behaviors of NSCLC cells. We also find that SGC3027 specifically activates ATM kinase and its downstream cell cycle checkpoint kinases to enhance radiobiological response in NSCLC. These findings underscore the promising therapeutic potential of PRMT7 inhibitors as well as combining PRMT7 inhibition with irradiation exposure for effective NSCLC therapies.

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PRMT7抑制剂SGC3027通过激活ATM激酶提高非小细胞肺癌的放疗疗效
非小细胞肺癌(NSCLC)是人类肿瘤相关死亡的主要原因。放疗是治疗非小细胞肺癌的关键策略,尽管其有效性受到肿瘤细胞放射耐药性的限制。我们目前的研究发现,蛋白精氨酸甲基转移酶7 (PRMT7)在NSCLC中表达上调,并与不良预后相关。特异性小分子PRMT7抑制剂SGC3027对PRMT7的药理抑制作用可抑制NSCLC的增殖、迁移和侵袭。与SGC3027联合照射可增强照射对NSCLC细胞生物学行为的影响。我们还发现SGC3027特异性激活ATM激酶及其下游细胞周期检查点激酶,以增强NSCLC的放射生物学应答。这些发现强调了PRMT7抑制剂的治疗潜力,以及将PRMT7抑制与辐射暴露相结合用于有效的非小细胞肺癌治疗。
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来源期刊
Radiation research
Radiation research 医学-核医学
CiteScore
5.10
自引率
8.80%
发文量
179
审稿时长
1 months
期刊介绍: Radiation Research publishes original articles dealing with radiation effects and related subjects in the areas of physics, chemistry, biology and medicine, including epidemiology and translational research. The term radiation is used in its broadest sense and includes specifically ionizing radiation and ultraviolet, visible and infrared light as well as microwaves, ultrasound and heat. Effects may be physical, chemical or biological. Related subjects include (but are not limited to) dosimetry methods and instrumentation, isotope techniques and studies with chemical agents contributing to the understanding of radiation effects.
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