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SDHA-mediated Warburg effect in malignantly transformed human bronchial epithelial cells following long-term exposure to radon
Environmental Toxicology ( IF 4.5 ) Pub Date : 2020-03-21 , DOI: 10.1002/tox.22922
Xing Liu 1, 2, 3 , Zongpeng Zhou 2 , Zikun Wang 2 , Xiangming Li 1, 2, 3 , Guangyu Lu 1, 2, 3 , Jian Tong 4
Affiliation  

Radon and its progeny have been classified as human class I carcinogens by the IARC. However, the mechanisms by which radon induces lung and other cancers, especially the radon‐induced Warburg effect, have not been fully elucidated. The aim of this study was to investigate the role of the succinate dehydrogenase subunit A (SDHA)‐mediated Warburg effect in (human bronchial epithelial) BEAS‐2B cells with malignant transformations induced by long‐term radon exposure. Soft agar colony formation and MMP‐9 were increased following radon‐induced malignant transformation. Additionally, we observed the Warburg effect in BEAS‐2B cells following long‐term radon exposure, evidenced by increases in the levels of glucose uptake, lactate, and lactate dehydrogenase (LDH). Following radon exposure, the expression of SDHA was decreased, while the levels of HIF‐1α and hexokinase‐2 (HK2) were increased. Our findings suggested that the SDHA‐associated pathway may be involved in mediating the Warburg effect in radon‐induced malignant transformation of BEAS‐2B.

中文翻译:

SDHA 介导的 Warburg 效应在长期暴露于氡后恶性转化的人支气管上皮细胞中

氡及其后代已被 IARC 列为人类 I 类致癌物。然而,氡诱导肺癌和其他癌症的机制,特别是氡诱导的Warburg效应,尚未完全阐明。本研究的目的是研究琥珀酸脱氢酶亚基 A(SDHA)介导的 Warburg 效应在(人支气管上皮)BEAS-2B 细胞中的作用,这些细胞具有由长期氡暴露诱导的恶性转化。氡诱导的恶性转化后软琼脂集落形成和 MMP-9 增加。此外,我们在长期氡暴露后观察到 BEAS-2B 细胞中的 Warburg 效应,这可以通过葡萄糖摄取、乳酸和乳酸脱氢酶 (LDH) 水平的增加来证明。氡暴露后,SDHA的表达降低,而 HIF-1α 和己糖激酶-2(HK2)的水平升高。我们的研究结果表明,SDHA 相关通路可能参与介导了氡诱导的 BEAS-2B 恶性转化中的 Warburg 效应。
更新日期:2020-03-21
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