Abstract
Cancer cells undergo substantial metabolic alterations to sustain increased energy supply and uncontrolled proliferation. As an essential trace element, iron is vital for many biological processes. Evidence has revealed that cancer cells deploy various mechanisms to elevate the cellular iron concentration to accelerate proliferation. Ferroptosis, a form of cell death caused by iron-catalyzed excessive peroxidation of polyunsaturated fatty acids (PUFAs), is a promising therapeutic target for therapy-resistant cancers. Previous studies have reported that long noncoding RNA (lncRNA) is a group of critical regulators involved in modulating cell metabolism, proliferation, apoptosis, and ferroptosis. In this review, we summarize the associations among iron metabolism, ferroptosis, and ferroptosis-related lncRNA in tumorigenesis. This information will help deepen understanding of the role of lncRNA in iron metabolism and raise the possibility of targeting lncRNA and ferroptosis in cancer combination therapy.
概要
代谢重编程是肿瘤标志性事件之一,癌细胞通过代谢重编程满足自身能量供应以及无限增殖。铁作为生命必要微量元素之一,对多种生物学过程包括DNA合成和修复、细胞呼吸、氧气运输、脂质氧化、信号转导等过程至关重要。研究表明,癌细胞通过多种机制增加细胞内铁离子浓度以促进细胞增殖。铁死亡是一种由铁催化的多不饱和脂肪酸过氧化引起的细胞死亡形式,是治疗耐药性肿瘤的潜在治疗靶点。长链非编码RNA(lncRNA)作为一种新型调控元件参与调节细胞代谢、增殖、凋亡和铁死亡等多种细胞过程。在本综述中,我们总结了铁代谢、铁死亡和lncRNA在肿瘤发生中的关系。深入探讨lncRNA在肿瘤铁死亡中的作用,将为联合靶向lncRNA和铁死亡相关分子在肿瘤治疗中提供新的策略和视角。
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Acknowledgments
This work was supported by the National Key Research and Development Program of China (No. 2021YFC2700903), the National Basic Research Program of China (No. 2017YFA01 05201), the National Natural Science Foundation of China (Nos. 81672791 and 81872300), the Zhejiang Provincial Natural Science Foundation of China for Distinguished Young Scholars (No. LR18C060002), the Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China (No. LHDMY22H160006), and the ZJU-QILU Joint Research Institute QILU Group.
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Aifu LIN and Jian LIU contributed to the study design and data analysis, and edited the manuscript. Lei QU and Xinyu HE wrote the manuscript. Lei QU, Qian TANG, and Xiao FAN contributed to the figure and table design. All authors have read and approved the final version.
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Lei QU, Xinyu HE, Qian TANG, Xiao FAN, Jian LIU, and Aifu LIN declare that they have no conflict of interest.
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Qu, L., He, X., Tang, Q. et al. Iron metabolism, ferroptosis, and lncRNA in cancer: knowns and unknowns. J. Zhejiang Univ. Sci. B 23, 844–862 (2022). https://doi.org/10.1631/jzus.B2200194
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DOI: https://doi.org/10.1631/jzus.B2200194