《生命科学》 2020, 32(10): 1099-1107

非编码RNA调控肿瘤细胞铁死亡分子机制的研究进展

陈　黎¹ , 唐旭东^1,2,*

¹广东医科大学生物化学与分子生物学研究所，湛江 524023 ²广东医科大学抗肿瘤活性物质研发协同创新中心，湛江 524023

摘　要：

铁死亡(ferroptosis)作为近年来新发现的一种在形态学、生化和遗传学等方面均区别于凋亡、坏死和自噬的调节性细胞死亡(regulated cell death, RDC)形式，是铁依赖的脂质活性氧(lipid reactive oxygen species, L-ROS)异常堆积诱导的细胞死亡。研究发现，铁死亡与肿瘤发展密切相关，微小RNA (microRNA, miRNA)、长链非编码RNA (long non-coding RNA, lncRNA)和环状RNA (circular RNA, circRNA)这三大类非编码RNA (non-coding RNA, ncRNA)可以通过转录或转录后水平调控肿瘤细胞铁死亡，其机制涉及谷氨酰胺分解、线粒体相关蛋白、铁代谢、谷胱甘肽代谢、脂质过氧化以及p53信号通路等。本文则围绕相关分子机制综述了ncRNA调控肿瘤细胞铁死亡的最新研究进展并展望了这一领域未来的发展方向，这将有助于指导基于铁死亡的肿瘤治疗干预。

通讯作者：唐旭东 , Email:tangxudong2599@126.com; txd@gdmu.edu.cn

Research progress on molecular mechanisms of non-coding RNA in regulating ferroptosis in tumor cells

CHEN Li¹ , TANG Xu-Dong^1,2,*

¹Institute of Biochemistry and Molecular Biology, Guangdong Medical University, Zhanjiang 524023, C ²Collaborative Innovation Center for Antitumor Active Substance Research and Development, Guangdong Medical University, Zhanjiang 524023, China

Abstract:

Ferroptosis, a novel regulated cell death (RCD) characterized by the iron-dependent accumulation of lipid reactive oxygen species (L-ROS) to abnormal levels, is different from apoptosis, necrosis and autophagy in morphology, biochemistry and genetics. Accumulating evidence demonstrates that ferroptosis plays an important role in tumor progression and the regulation of ferroptosis is tightly linked to non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). NcRNAs can regulate ferroptosis in tumor cells at transcriptional or post-transcriptional levels, and the underlying mechanisms are related to glutaminolysis, mitochondrial related proteins, iron metabolism, glutathione metabolism, lipid peroxidation and p53 signaling pathways, etc. This review summarized the molecular mechanisms of ncRNAs in regulating ferroptosis in tumor cells and looked forward to the future research direction in this field, which will contribute to the guidance for tumor intervention based on ferroptosis.

Communication Author：TANG Xu-Dong , Email:tangxudong2599@126.com; txd@gdmu.edu.cn