对辐射敏感的circRNA hsa_circ_0096498通过抑制EIF4A3核转位来抑制辐射诱导的肝纤维化,从而降低肝星细胞中CDC42的表达
Peitao Zhou1,2, Yixun Deng3, Yining Sun1,2
1Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510515, China.
Journal of translational medicine
|October 1, 2024
概括
这项研究确定circ96498是通过抑制肝星细胞激活来预防辐射诱导肝纤维化的一个关键调节剂. 针对circ96498/EIF4A3/CDC42途径为RILF提供了一个新的治疗策略.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 辐射诱导性肝纤维化 (RILF) 是放射治疗的严重并发症,主要是由激活的肝星细胞 (HSC) 驱动的.
- 循环RNAs (circRNAs) 在RILF病变发生中的作用在很大程度上仍未被探索.
研究的目的:
- 研究放射诱导性肝损伤 (RILI) 和随后的纤维化中的circRNAs的功能和机制.
- 确定在RILF期间参与调节肝星细胞激活的特定circRNAs.
主要方法:
- RNA下拉,LC-MS/MS和RNA免疫沉以确定circRNA-蛋白相互作用.
- RNA测序以确定circRNA调节的基因表达.
- 在体外测试中使用HSC和体内RILF小鼠模型来评估circ96498和CDC42调制的治疗潜力.
主要成果:
- 一种新的对辐射敏感的circRNA,hsa_circ_0096498 (circ96498),被确定并被发现在被辐射的HSC上升调节.
- Circ96498 抑制 HSC 增殖,促进细胞灭绝,减少促炎性细胞因子,并抑制益菌性标记物.
- 在机械上,circ96498与EIF4A3结合,防止核转位和随后的CDC42mRNA稳定,从而通过NF-κB和JNK/Smad2通路抑制HSC激活.
结论:
- 该circ96498/EIF4A3/CDC42轴在抑制辐射诱导的HSC激活方面发挥着至关重要的作用.
- Circ96498充当了对RILF的保护因素.
- 这个轴的调节为预防和治疗RILF提供了一个有希望的治疗途径.
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