Iron Metabolism, Ferroptosis, and LncRNA in Cancer: Knowns and Unknowns

Overview

Journal J Zhejiang Univ Sci B

Specialties Biology
General Medicine

Date 2022 Oct 13

PMID 36226538

Authors

Lei Qu

Xinyu He

Qian Tang

Xiao Fan

Jian Liu

Aifu Lin

Affiliations

Soon will be listed here.

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.

Citing Articles

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References

Osborne N, Gurrin L, Allen K, Constantine C, Delatycki M, McLaren C . HFE C282Y homozygotes are at increased risk of breast and colorectal cancer. Hepatology. 2010; 51(4):1311-8. PMC: 3815603. DOI: 10.1002/hep.23448. View

Muto Y, Moroishi T, Ichihara K, Nishiyama M, Shimizu H, Eguchi H . Disruption of FBXL5-mediated cellular iron homeostasis promotes liver carcinogenesis. J Exp Med. 2019; 216(4):950-965. PMC: 6446870. DOI: 10.1084/jem.20180900. View

Xue X, Bredell B, Anderson E, Martin A, Mays C, Nagao-Kitamoto H . Quantitative proteomics identifies STEAP4 as a critical regulator of mitochondrial dysfunction linking inflammation and colon cancer. Proc Natl Acad Sci U S A. 2017; 114(45):E9608-E9617. PMC: 5692584. DOI: 10.1073/pnas.1712946114. View

Netz D, Stith C, Stumpfig M, Kopf G, Vogel D, Genau H . Eukaryotic DNA polymerases require an iron-sulfur cluster for the formation of active complexes. Nat Chem Biol. 2011; 8(1):125-32. PMC: 3241888. DOI: 10.1038/nchembio.721. View

Wang K, Chang H . Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011; 43(6):904-14. PMC: 3199020. DOI: 10.1016/j.molcel.2011.08.018. View

Khan M, Walden W, Goss D, Theil E . Direct Fe2+ sensing by iron-responsive messenger RNA:repressor complexes weakens binding. J Biol Chem. 2009; 284(44):30122-8. PMC: 2781567. DOI: 10.1074/jbc.M109.041061. View

Gu Z, Wang H, Xia J, Yang Y, Jin Z, Xu H . Decreased ferroportin promotes myeloma cell growth and osteoclast differentiation. Cancer Res. 2015; 75(11):2211-21. PMC: 4946247. DOI: 10.1158/0008-5472.CAN-14-3804. View

Koppula P, Zhang Y, Zhuang L, Gan B . Amino acid transporter SLC7A11/xCT at the crossroads of regulating redox homeostasis and nutrient dependency of cancer. Cancer Commun (Lond). 2018; 38(1):12. PMC: 5993148. DOI: 10.1186/s40880-018-0288-x. View

Zhang Y, Shi J, Liu X, Feng L, Gong Z, Koppula P . BAP1 links metabolic regulation of ferroptosis to tumour suppression. Nat Cell Biol. 2018; 20(10):1181-1192. PMC: 6170713. DOI: 10.1038/s41556-018-0178-0. View

10.

Fox A, Nakagawa S, Hirose T, Bond C . Paraspeckles: Where Long Noncoding RNA Meets Phase Separation. Trends Biochem Sci. 2018; 43(2):124-135. DOI: 10.1016/j.tibs.2017.12.001. View

11.

Johnsen K, Burkhart A, Thomsen L, Andresen T, Moos T . Targeting the transferrin receptor for brain drug delivery. Prog Neurobiol. 2019; 181:101665. DOI: 10.1016/j.pneurobio.2019.101665. View

12.

Daniels T, Bernabeu E, Rodriguez J, Patel S, Kozman M, Chiappetta D . The transferrin receptor and the targeted delivery of therapeutic agents against cancer. Biochim Biophys Acta. 2011; 1820(3):291-317. PMC: 3500658. DOI: 10.1016/j.bbagen.2011.07.016. View

13.

Okazaki F, Matsunaga N, Okazaki H, Utoguchi N, Suzuki R, Maruyama K . Circadian rhythm of transferrin receptor 1 gene expression controlled by c-Myc in colon cancer-bearing mice. Cancer Res. 2010; 70(15):6238-46. DOI: 10.1158/0008-5472.CAN-10-0184. View

14.

Ohgami R, Campagna D, Greer E, Antiochos B, McDonald A, Chen J . Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. Nat Genet. 2005; 37(11):1264-9. PMC: 2156108. DOI: 10.1038/ng1658. View

15.

Vela D, Vela-Gaxha Z . Differential regulation of hepcidin in cancer and non-cancer tissues and its clinical implications. Exp Mol Med. 2018; 50(2):e436. PMC: 5903825. DOI: 10.1038/emm.2017.273. View

16.

Liu J, Xia X, Huang P . xCT: A Critical Molecule That Links Cancer Metabolism to Redox Signaling. Mol Ther. 2020; 28(11):2358-2366. PMC: 7647670. DOI: 10.1016/j.ymthe.2020.08.021. View

17.

Liu X, Liang Y, Song R, Yang G, Han J, Lan Y . Long non-coding RNA NEAT1-modulated abnormal lipolysis via ATGL drives hepatocellular carcinoma proliferation. Mol Cancer. 2018; 17(1):90. PMC: 5953401. DOI: 10.1186/s12943-018-0838-5. View

18.

Zhang K, Ping L, Du T, Liang G, Huang Y, Li Z . A Ferroptosis-Related lncRNAs Signature Predicts Prognosis and Immune Microenvironment for Breast Cancer. Front Mol Biosci. 2021; 8:678877. PMC: 8215711. DOI: 10.3389/fmolb.2021.678877. View

19.

Hung C, Wang L, Yu Y, Chen H, Srivastava S, Petrovics G . A long noncoding RNA connects c-Myc to tumor metabolism. Proc Natl Acad Sci U S A. 2014; 111(52):18697-702. PMC: 4284533. DOI: 10.1073/pnas.1415669112. View

20.

Pasricha S, Tye-Din J, Muckenthaler M, Swinkels D . Iron deficiency. Lancet. 2020; 397(10270):233-248. DOI: 10.1016/S0140-6736(20)32594-0. View