环状RNA调控肿瘤细胞铁死亡的研究进展

Progress in regulation of ferroptosis by circular RNA in tumor cells

铁死亡是铁离子依赖的脂质过氧化物累积引起的一种不同于细胞坏死、凋亡和自噬的新的程序性细胞死亡方式[1]。溶质载体家族7成员11(solute carrier family 7 member 11,SLC7A11)、谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)、二氢乳清酸脱氢酶(dihydroorotate dehydrogenase,DHODH)和线粒体相关凋亡诱导因子2(apoptosis-inducing factor mitochondria-associated 2,AIFM2)是目前发现的调控细胞铁死亡的关键基因。SLC7A11和SLC3A2共同组成谷氨酸/胱氨酸反向转运体,负责将胱氨酸由细胞外运输进入细胞内用于谷胱甘肽的合成,是铁死亡的负调控因子[2]。GPX4通过特异性催化谷胱甘肽将脂质过氧化物转化为类脂醇,发挥抑制细胞铁死亡的作用[3]。DHODH通过抑制线粒体内脂质过氧化过程而抑制细胞铁死亡的发生[4]。

Ferroptosis is a newly identified type of programmed cell death caused by the accumulation of irondependent lipid peroxides. Ferroptosis plays a critical role in tumor suppression,thus providing new opportunities for treatment of cancer. Circular RNA(circRNA)is a type of closed circular non-coding RNA molecules without 5’-terminal cap and 3’-terminal poly(A). circRNA regulates the expression of key molecules involved in ferroptosis such as GPX4,SLC7A11 and AIFM2 by directly binding to microRNA(miRNA),and regulates the ferroptosis of tumor cells by binding and regulating related proteins. Studying and revealing the molecular mechanisms of circRNA in regulating ferroptosis of tumor cells will help to develop new anti-tumor therapies based on circRNA-induced ferroptosis.