circFAM134B是肝细胞癌中网膜化介导铁化调节的一个关键因素
Tao Bi1,2, Qianqian Lu3, Xiaohong Pan4
1Department of Hepatobiliary Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.
Cell cycle (Georgetown, Tex.)
|August 21, 2023
概括
循环RNAcircFAM134B通过向ER-phagy来促进在肝细胞癌中由lenvatinib诱导的ferroptosis. 这一发现揭示了一个新的circFAM134B-PABPC4-FAM134B轴,为HCC提供了新的治疗策略.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 在瘤学瘤学.
背景情况:
- 铁亡是一种受调节的细胞死亡 (RCD) 模式,对于肝细胞癌 (HCC) 的进展和治疗耐药性至关重要.
- 选择性自,包括ER-phagy,在铁中起作用,特别是在用氨酸激酶抑制剂 (TKIs) 治疗的HCC中.
研究的目的:
- 为了研究循环RNA hsa_circ_0128505 (circFAM134B) 在伦巴替尼 (LV) 诱导的HCC细胞铁亡中的作用.
- 阐明涉及ER-phagy和circFAM134B-PABPC4-FAM134B轴的潜在分子机制.
主要方法:
- 使用反应性氧物种 (ROS),Fe2+, (MDA) 和西部斑点 (WB) 试验来评估铁亡.
- 采用RNA下拉,质谱,RNA免疫沉 (RIP) 和光酶记者测试来识别和验证蛋白质相互作用和机制.
主要成果:
- 鉴定circFAM134B作为一种特定诱导ER-phagy介导的HCC细胞中治疗lenvatinib的ferroptosis.
- 发现circFAM134B具有竞争性地与PABPC4结合,作为一种海绵,可以抑制FAM134BmRNA的无意义介导mRNA衰变 (NMD).
- 确定了circFAM134B-PABPC4-FAM134B轴作为HCC中铁亡的关键调节器.
结论:
- circFAM134B通过FAM134BmRNA的PABPC4介导的NMD通路调节ER-phagy,促进lenvatinib诱导的HCC中的铁亡.
- 环FAM134B-PABPC4-FAM134B轴代表了综合性HCC治疗的新型治疗标.
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