外基因源的circUPF2通过重新部署肝细胞癌中的ferroptosis敏感性来增强对向治疗的耐药性
Feng-Lin Dong1,2, Zong-Zhen Xu1, Ying-Qiao Wang3
1Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Shandong Provincial Qianfoshan Hospital, No. 16766, Jingshi Road, Jinan, 250014, China.
Journal of nanobiotechnology
|May 29, 2024
概括
外体circUPF2通过稳定SLC7A11mRNA,抑制铁亡,促进肝细胞癌 (HCC) 中的索拉芬尼抗性. 向外体环UPF2为HCC治疗提供了一个新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 晚期肝细胞癌 (HCC) 治疗依赖于索拉费尼布,但耐药性限制了疗效.
- 外体和圆形RNA与癌症进展有关,但它们在HCC索拉芬尼布耐药性中的作用尚不清楚.
研究的目的:
- 调查外体循环RNAs在HCC. sorafenib耐药性的发展中的作用.
- 阐明外体circUPF2在介导HCC耐药性的基础分子机制.
主要方法:
- 从抗索拉尼布的HCC细胞中分离出外体 (Exo-SR).
- 转录组测序以识别差异表达的基因和外体标.
- 功能增益和丧失实验,以评估circUPF2对索拉费尼布耐药性的影响.
- RNA下拉,质谱,RIP和FISH测试用于验证分子相互作用.
主要成果:
- 一种新型的外体 circRNA,circUPF2,被确定并以 Exo-SR.丰富.
- 外体circUPF2通过促进SLC7A11表达和抑制铁亡来增强索拉芬尼抗性.
- CircUPF2通过与IGF2BP2和SLC7A11形成三元复合体来稳定SLC7A11mRNA,从而增强系统Xc-功能.
结论:
- 外体circUPF2通过circUPF2-IGF2BP2-SLC7A11复合体促进HCC中的索拉芬尼抗性.
- 向外体环UPF2为HCC提供了一个潜在的创新治疗策略.
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