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Circ_0008657通过miR-203a-3p/ATM轴调节六价引起的肺DNA损伤

Wei Chen¹, Zehao Chen¹, Yangyang Jia²

¹The Key Laboratory of Advanced Interdisciplinary Studies, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China; Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 511436, China.

Environment international

|February 23, 2024

概括

六价 (Cr VI) 暴露会导致肺细胞DNA受损. 一种特定的圆形RNA,circ_0008657,通过干扰microRNA-203a-3p和ATM DNA修复途径,加剧了这种损伤.

科学领域:

环境健康环境健康
分子生物学分子生物学
毒理学毒理学毒理学

背景情况:

六价 (Cr VI) 是一种与肺损伤有关的环境污染物.
Cr VI是遗传毒性,通过不清楚的表观遗传机制引起DNA损伤.

研究的目的:

研究人类肺细胞中Cr VI诱导的DNA损伤的表观遗传机制.
为了确定对CrVI暴露的DNA损伤反应中的关键分子参与者.

主要方法:

在人类支气管上皮细胞 (16HBE,BEAS-2B) 和小鼠肺组织中利用了Cr VI (0-10μM) 的新型暴露剂量计算.
进行彗星测定和测量橄尾时刻,以评估DNA损伤.
分析了circ_0008657的作用及其与miR-203a-3p和ATM信号的相互作用.

主要成果:

暴露于Cr VI显著增加了DNA损伤,由彗星测定和γ-H2AX焦点证明.
Circ_0008657的升高与Cr VI诱导的DNA损伤相关.
敲击circ_0008657减少了DNA损伤,而过度表达增加了它.
在机械上,circ_0008657具有竞争性地与miR-203a-3p结合,影响ATM通路的激活.

结论:

Circ_0008657在调解Cr VI诱导的DNA损伤方面发挥着至关重要的作用.
该circ_0008657/miR-203a-3p/ATM轴是细胞对Cr VI暴露反应的一个关键途径.
研究结果提供了对环境污染物对DNA损伤的表观遗传调节的见解.

关键词:

这是循环RNARNA.造成的DNA损伤是DNA损伤.六价的六价是一种这是一个微型RNA.

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