Liu Min-Yao, Li Hong-Ming, Wang Xin-Yu, Xia Ran, Li Xiang, Ma Yu-Jie, Wang Miao, Zhang Hong-Sheng
Faculty of Environment and Life, Beijing University of Technology, Pingleyuan 100(#), District of Chaoyang, Beijing, 100124, China.
Faculty of Environment and Life, Beijing University of Technology, Pingleyuan 100(#), District of Chaoyang, Beijing, 100124, China.
Free Radic Biol Med. 2022 Mar;182:219-231. doi: 10.1016/j.freeradbiomed.2022.03.002. Epub 2022 Mar 7.
Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and major cause of cancer death in the world. Ferroptosis is a recently identified type of regulated cell death. Increasing evidence has shown that ferroptosis plays an important regulatory role in the occurrence and development of cancer. This study identified TIGAR as a potential regulator of ferroptosis resistance in the development of CRC. We showed that TIGAR expression in CRC tissues is significantly higher than that in adjacent normal tissues. Knockdown of TIGAR significantly caused an increase in erastin-induced ferroptosis in SW620 and HCT116 cells. Notably, knockdown of TIGAR significantly decreased GSH/GSSG ratio, increased lipid peroxidation production, and facilitated the accumulation of lipid peroxidation product malondialdehyde (MDA), and rendered CRC cells more sensitive to erastin induced ferroptosis. Furthermore, TIGAR inhibition repressed SCD1 expression in a redox and AMPK-dependent manner. Thus, these results suggest that TIGAR induces ferroptosis resistance in CRC cells via the ROS/AMPK/SCD1 signaling pathway.
结直肠癌（CRC）是全球第三大最常被诊断出的恶性肿瘤，也是癌症死亡的主要原因。铁死亡是一种最近被发现的程序性细胞死亡类型。越来越多的证据表明，铁死亡在癌症的发生和发展中起着重要的调节作用。本研究确定TIGAR是CRC发生发展过程中铁死亡抗性的潜在调节因子。我们发现，CRC组织中TIGAR的表达明显高于相邻正常组织。敲低TIGAR显著导致SW620和HCT116细胞中erastin诱导的铁死亡增加。值得注意的是，敲低TIGAR显著降低了谷胱甘肽/氧化型谷胱甘肽（GSH/GSSG）比值，增加了脂质过氧化产物的生成，并促进了脂质过氧化产物丙二醛（MDA）的积累，使CRC细胞对erastin诱导的铁死亡更敏感。此外，TIGAR抑制以氧化还原和AMPK依赖性方式抑制硬脂酰辅酶A去饱和酶1（SCD1）的表达。因此，这些结果表明，TIGAR通过活性氧/AMPK/SCD1信号通路诱导CRC细胞的铁死亡抗性。
