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.

癌症中的铁代谢、铁死亡和长链非编码RNA：已知与未知

[1]AlkhateebAA, HanB, ConnorJR, 2013. Ferritin stimulates breast cancer cells through an iron-independent mechanism and is localized within tumor-associated macrophages. Breast Cancer Res Treat, 137(3):733-744.

[2]AlvarezSW, SviderskiyVO, TerziEM, et al., 2017. NFS1 undergoes positive selection in lung tumours and protects cells from ferroptosis. Nature, 551(7682):639-643.

[3]BarnesJL, ZubairM, JohnK, et al., 2018. Carcinogens and DNA damage. Biochem Soc Trans, 46(5):1213-1224.

[4]BellRJA, RubeHT, KreigA, et al., 2015. The transcription factor GABP selectively binds and activates the mutant TERT promoter in cancer. Science, 348(6238):1036-1039.

[5]BergerT, CheungCC, EliaAJ, et al., 2010. Disruption of the Lcn2 gene in mice suppresses primary mammary tumor formation but does not decrease lung metastasis. Proc Natl Acad Sci USA, 107(7):2995-3000.

[6]BerkersCR, MaddocksODK, CheungEC, et al., 2013. Metabolic regulation by p53 family members. Cell Metab, 18(5):617-633.

[7]BillesbølleCB, AzumayaCM, KretschRC, et al., 2020. Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms. Nature, 586(7831):807-811.

[8]BogdanAR, MiyazawaM, HashimotoK, et al., 2016. Regulators of iron homeostasis: new players in metabolism, cell death, and disease. Trends Biochem Sci, 41(3):274-286.

[9]Brigelius-FlohéR, MaiorinoM, 2013. Glutathione peroxidases. Biochim Biophys Acta (BBA)‒Gen Subj, 1830(5):3289-3303.

[10]BrookesMJ, HughesS, TurnerFE, et al., 2006. Modulation of iron transport proteins in human colorectal carcinogenesis. Gut, 55(10):1449-1460.

[11]CallensC, MouraIC, LepelletierY, et al., 2008. Recent advances in adult T-cell leukemia therapy: focus on a new anti-transferrin receptor monoclonal antibody. Leukemia, 22(1):42-48.

[12]CarrieriC, CimattiL, BiagioliM, et al., 2012. Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat. Nature, 491(7424):454-457.

[13]Challita-EidPM, MorrisonK, EtessamiS, et al., 2007. Monoclonal antibodies to six-transmembrane epithelial antigen of the prostate-1 inhibit intercellular communication in vitro and growth of human tumor xenografts in vivo. Cancer Res, 67(12):5798-5805.

[14]ChekhunVF, LukyanovaNY, BurlakaAP, et al., 2013. Iron metabolism disturbances in the MCF-7 human breast cancer cells with acquired resistance to doxorubicin and cisplatin. Int J Oncol, 43(5):1481-1486.

[15]ChenDL, TavanaO, ChuB, et al., 2017. NRF2 is a major target of ARF in p53-independent tumor suppression. Mol Cell, 68(1):224-232.e4.

[16]ChenPH, WuJL, DingCKC, et al., 2020. Kinome screen of ferroptosis reveals a novel role of ATM in regulating iron metabolism. Cell Death Differ, 27(3):1008-1022.

[17]ChenW, ParadkarPN, LiLT, et al., 2009. Abcb10 physically interacts with mitoferrin-1 (Slc25a37) to enhance its stability and function in the erythroid mitochondria. Proc Natl Acad Sci USA, 106(38):16263-16268.

[18]ChenX, YuCH, KangR, et al., 2021. Cellular degradation systems in ferroptosis. Cell Death Differ, 28(4):1135-1148.

[19]ChenZA, TianH, YaoDM, et al., 2021. Identification of a ferroptosis-related signature model including mRNAs and lncRNAs for predicting prognosis and immune activity in hepatocellular carcinoma. Front Oncol, 11:738477.

[20]ChengGC, SunXQ, WangJL, et al., 2014. HIC1 silencing in triple-negative breast cancer drives progression through misregulation of LCN2. Cancer Res, 74(3):862-872.

[21]ChiYD, RemsikJ, KiseliovasV, et al., 2020. Cancer cells deploy lipocalin-2 to collect limiting iron in leptomeningeal metastasis. Science, 369(6501):276-282.

[22]ChuB, KonN, ChenDL, et al., 2019. ALOX12 is required for p53-mediated tumour suppression through a distinct ferroptosis pathway. Nat Cell Biol, 21(5):579-591.

[23]CinelliMA, DoHT, MileyGP, et al., 2020. Inducible nitric oxide synthase: regulation, structure, and inhibition. Med Res Rev, 40(1):158-189.

[24]ConradM, PrattDA, 2019. The chemical basis of ferroptosis. Nat Chem Biol, 15(12):1137-1147.

[25]CrielaardBJ, LammersT, RivellaS, 2017. Targeting iron metabolism in drug discovery and delivery. Nat Rev Drug Discov, 16(6):400-423.

[26]DanielsTR, BernabeuE, RodríguezJA, et al., 2012. The transferrin receptor and the targeted delivery of therapeutic agents against cancer. Biochim Biophys Acta (BBA)‒Gen Subj, 1820(3):291-317.

[27]DixonSJ, StockwellBR, 2014. The role of iron and reactive oxygen species in cell death. Nat Chem Biol, 10(1):9-17.

[28]DixonSJ, LembergKM, LamprechtMR, et al., 2012. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell, 149(5):1060-1072.

[29]DixonSJ, WinterGE, MusaviLS, et al., 2015. Human haploid cell genetics reveals roles for lipid metabolism genes in nonapoptotic cell death. ACS Chem Biol, 10(7):1604-1609.

[30]DodsonM, Castro-PortuguezR, ZhangDD, 2019. NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis. Redox Biol, 23:101107.

[31]DollS, PronethB, TyurinaYY, et al., 2017. ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat Chem Biol, 13(1):91-98.

[32]dos SantosMCF, AndersonCP, NeschenS, et al., 2020. Irp2 regulates insulin production through iron-mediated Cdkal1-catalyzed tRNA modification. Nat Commun, 11:296.

[33]DrakesmithH, NemethE, GanzT, 2015. Ironing out ferroportin. Cell Metab, 22(5):777-787.

[34]DuJ, ZhouY, LiYC, et al., 2020. Identification of Frataxin as a regulator of ferroptosis. Redox Biol, 32:101483.

[35]DufrusineB, di FrancescoA, OddiS, et al., 2019. Iron-dependent trafficking of 5-lipoxygenase and impact on human macrophage activation. Front Immunol, 10:1347.

[36]FengHZ, SchorppK, JinJ, et al., 2020. Transferrin receptor is a specific ferroptosis marker. Cell Rep, 30(10):‍3411-3423.e7.

[37]FoxAH, NakagawaS, HiroseT, et al., 2018. Paraspeckles: where long noncoding RNA meets phase separation. Trends Biochem Sci, 43(2):124-135.

[38]GaiCC, LiuCL, WuXH, et al., 2020. MT1DP loaded by folate-modified liposomes sensitizes erastin-induced ferroptosis via regulating miR-365a-3p/NRF2 axis in non-small cell lung cancer cells. Cell Death Discov, 11(9):751.

[39]GaoMH, MonianP, QuadriN, et al., 2015. Glutaminolysis and transferrin regulate ferroptosis. Mol Cell, 59(2):298-308.

[40]GaoMH, MonianP, PanQH, et al., 2016. Ferroptosis is an autophagic cell death process. Cell Res, 26(9):1021-1032.

[41]GaoMH, YiJM, ZhuJJ, et al., 2019. Role of mitochondria in ferroptosis. Mol Cell, 73(2):354-363.e3.

[42]GariK, León OrtizAM, BorelV, et al., 2012. MMS19 links cytoplasmic iron-sulfur cluster assembly to DNA metabolism. Science, 337(6091):243-245.

[43]GoldbergAV, MolikS, TsaousisAD, et al., 2008. Localization and functionality of microsporidian iron-sulphur cluster assembly proteins. Nature, 452(7187):624-628.

[44]Gomez-ChouSB, Swidnicka-SiergiejkoAK, BadiN, et al., 2017. Lipocalin-2 promotes pancreatic ductal adenocarcinoma by regulating inflammation in the tumor microenvironment. Cancer Res, 77(10):2647-2660.

[45]GozzelinoR, JeneyV, SoaresMP, 2010. Mechanisms of cell protection by heme oxygenase-1. Annu Rev Pharmacol Toxicol, 50:323-354.

[46]GuZM, WangH, XiaJL, et al., 2015. Decreased ferroportin promotes myeloma cell growth and osteoclast differentiation. Cancer Res, 75(11):2211-2221.

[47]GuoCJ, MaXK, XingYH, et al., 2020. Distinct processing of lncRNAs contributes to non-conserved functions in stem cells. Cell, 181(3):621-636.e22.

[48]HangauerMJ, ViswanathanVS, RyanMJ, et al., 2017. Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition. Nature, 551(7679):247-250.

[49]HassanniaB, WiernickiB, IngoldI, et al., 2018. Nano-targeted induction of dual ferroptotic mechanisms eradicates high-risk neuroblastoma. J Clin Invest, 128(8):3341-3355.

[50]HassanniaB, VandenabeeleP, Vanden BergheT, 2019. Targeting ferroptosis to iron out cancer. Cancer Cell, 35(6):830-849.

[51]HayanoM, YangWS, CornCK, et al., 2016. Loss of cysteinyl-tRNA synthetase (CARS) induces the transsulfuration pathway and inhibits ferroptosis induced by cystine deprivation. Cell Death Differ, 23(2):270-278.

[52]HayesJD, Dinkova-KostovaAT, 2017. Epigenetic control of NRF2-directed cellular antioxidant status in dictating life-death decisions. Mol Cell, 68(1):5-7.

[53]HentzeMW, MuckenthalerMU, GalyB, et al., 2010. Two to tango: regulation of mammalian iron metabolism. Cell, 142(1):24-38.

[54]HorniblowRD, BedfordM, HollingworthR, et al., 2017. BRAF mutations are associated with increased iron regulatory protein-2 expression in colorectal tumorigenesis. Cancer Sci, 108(6):1135-1143.

[55]HouW, XieYC, SongXX, et al., 2016. Autophagy promotes ferroptosis by degradation of ferritin. Autophagy, 12(8):1425-1428.

[56]HungCL, WangLY, YuYL, et al., 2014. A long noncoding RNA connects c-Myc to tumor metabolism. Proc Natl Acad Sci USA, 111(52):18697-18702.

[57]JiangL, KonN, LiTY, et al., 2015. Ferroptosis as a p53-mediated activity during tumour suppression. Nature, 520(7545):57-62.

[58]JiangXJ, StockwellBR, ConradM, 2021. Ferroptosis: mechanisms, biology and role in disease. Nat Rev Mol Cell Biol, 22(4):266-282.

[59]JohnsenKB, BurkhartA, ThomsenLB, et al., 2019. Targeting the transferrin receptor for brain drug delivery. Prog Neurobiol, 181:101665.

[60]JonesDT, TrowbridgeIS, HarrisAL, 2006. Effects of transferrin receptor blockade on cancer cell proliferation and hypoxia-inducible factor function and their differential regulation by ascorbate. Cancer Res, 66(5):2749-2756.

[61]JunttilaMR, EvanGI, 2009. p53—a Jack of all trades but master of none. Nat Rev Cancer, 9(11):821-829.

[62]KaganVE, MaoGW, QuF, et al., 2017. Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis. Nat Chem Biol, 13(1):81-90.

[63]KastenhuberER, LoweSW, 2017. Putting p53 in context. Cell, 170(6):1062-1078.

[64]KeelSB, DotyRT, YangZT, et al., 2008. A heme export protein is required for red blood cell differentiation and iron homeostasis. Science, 319(5864):825-828.

[65]KhanMA, WaldenWE, GossDJ, et al., 2009. Direct Fe²⁺ sensing by iron-responsive messenger RNA·repressor complexes weakens binding. J Biol Chem, 284(44):30122-30128.

[66]KobayashiH, NagatoT, SatoK, et al., 2007. Recognition of prostate and melanoma tumor cells by six-transmembrane epithelial antigen of prostate-specific helper T lymphocytes in a human leukocyte antigen class II-restricted manner. Cancer Res, 67(11):5498-5504.

[67]KoppulaP, ZhangYL, ZhuangL, et al., 2018. Amino acid transporter SLC7A11/xCT at the crossroads of regulating redox homeostasis and nutrient dependency of cancer. Cancer Commun (Lond), 38(1):1-13.

[68]KorolnekT, HamzaI, 2015. Macrophages and iron trafficking at the birth and death of red cells. Blood, 125(19):2893-2897.

[69]LengXH, DingT, LinH, et al., 2009. Inhibition of lipocalin 2 impairs breast tumorigenesis and metastasis. Cancer Res, 69(22):8579-8584.

[70]LiDS, LiYS, 2020. The interaction between ferroptosis and lipid metabolism in cancer. Signal Transduct Target Ther, 5:108.

[71]LiQQ, LiQ, JiaJN, et al., 2018. 12/15 lipoxygenase: a crucial enzyme in diverse types of cell death. Neurochem Int, 118:34-41.

[72]LiRH, TianT, GeQW, et al., 2021. A phosphatidic acid-binding lncRNA SNHG9 facilitates LATS1 liquid-liquid phase separation to promote oncogenic YAP signaling. Cell Res, 31(10):1088-1105.

[73]LiYJ, TanZ, ZhangYH, et al., 2021. A noncoding RNA modulator potentiates phenylalanine metabolism in mice. Science, 373(6555):662-673.

[74]LillR, FreibertSA, 2020. Mechanisms of mitochondrial iron-sulfur protein biogenesis. Annu Rev Biochem, 89:471-499.

[75]LinAF, LiCL, XingZ, et al., 2016. The LINK-A lncRNA activates normoxic HIF1α signalling in triple-negative breast cancer. Nat Cell Biol, 18(2):213-224.

[76]LinAF, HuQS, LiCL, et al., 2017. The LINK-A lncRNA interacts with PtdIns(3,4,5)P₃ to hyperactivate AKT and confer resistance to AKT inhibitors. Nat Cell Biol, 19(3):238-251.

[77]LinCR, YangLQ, 2018. Long noncoding RNA in cancer: wiring signaling circuitry. Trends Cell Biol, 28(4):287-301.

[78]LinehanWM, RouaultTA, 2013. Molecular pathways: fumarate hydratase-deficient kidney cancer—targeting the Warburg effect in cancer. Clin Cancer Res, 19(13):‍3345-3352.

[79]LiuJ, LiuZX, WuQN, et al., 2020. Long noncoding RNA AGPG regulates PFKFB3-mediated tumor glycolytic reprogramming. Nat Commun, 11:1507.

[80]LiuJH, GaoL, ZhanN, et al., 2020. Hypoxia induced ferritin light chain (FTL) promoted epithelia mesenchymal transition and chemoresistance of glioma. J Exp Clin Cancer Res, 39:137.

[81]LiuJY, XiaXJ, HuangP, 2020. xCT: a critical molecule that links cancer metabolism to redox signaling. Mol Ther, 28(11):2358-2366.

[82]LiuSJ, DangHX, LimDA, et al., 2021. Long noncoding RNAs in cancer metastasis. Nat Rev Cancer, 21(7):446-460.

[83]LiuXR, LiangYJ, SongRP, et al., 2018. Long non-coding RNA NEAT1-modulated abnormal lipolysis via ATGL drives hepatocellular carcinoma proliferation. Mol Cancer, 17:90.

[84]LoM, WangYZ, GoutPW, 2008. The xc- cystine/glutamate antiporter: a potential target for therapy of cancer and other diseases. J Cell Physiol, 215(3):593-602.

[85]LuL, LiuLP, ZhaoQQ, et al., 2021. Identification of a ferroptosis-related lncRNA signature as a novel prognosis model for lung adenocarcinoma. Front Oncol, 11:675545.

[86]LuoWJ, WangJ, XuWH, et al., 2021. LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer. Cell Death Discov, 12(11):1043.

[87]MaJ, HaldarS, KhanMA, et al., 2012. Fe²⁺ binds iron responsive element-RNA, selectively changing protein-binding affinities and regulating mRNA repression and activation. Proc Natl Acad Sci USA, 109(22):8417-8422.

[88]MaQ, 2013. Role of Nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol, 53:401-426.

[89]MalakarP, SteinI, SaragoviA, et al., 2019. Long noncoding RNA MALAT1 regulates cancer glucose metabolism by enhancing mTOR-mediated translation of TCF7L2. Cancer Res, 79(10):2480-2493.

[90]ManciasJD, WangXX, GygiSP, et al., 2014. Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. Nature, 509(7498):105-109.

[91]MaoC, WangX, LiuYT, et al., 2018. A G3BP1-interacting lncRNA promotes ferroptosis and apoptosis in cancer via nuclear sequestration of p53. Cancer Res, 78(13):‍3484-3496.

[92]Meyron-HoltzEG, GhoshMC, RouaultTA, 2004. Mammalian tissue oxygen levels modulate iron-regulatory protein activities in vivo. Science, 306(5704):2087-2090.

[93]MillerLD, CoffmanLG, ChouJW, et al., 2011. An iron regulatory gene signature predicts outcome in breast cancer. Cancer Res, 71(21):6728-6737.

[94]MuckenthalerMU, GalyB, HentzeMW, 2008. Systemic iron homeostasis and the iron-responsive element/iron-regulatory protein (IRE/IRP) regulatory network. Annu Rev Nutr, 28:197-213.

[95]MuckenthalerMU, RivellaS, HentzeMW, et al., 2017. A red carpet for iron metabolism. Cell, 168(3):344-361.

[96]MutoY, MoroishiT, IchiharaK, et al., 2019. Disruption of FBXL5-mediated cellular iron homeostasis promotes liver carcinogenesis. J Exp Med, 216(4):950-965.

[97]NetzDJA, StithCM, StümpfigM, et al., 2011. Eukaryotic DNA polymerases require an iron-sulfur cluster for the formation of active complexes. Nat Chem Biol, 8(1):125-132.

[98]OhgamiRS, CampagnaDR, GreerEL, et al., 2005. Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. Nat Genet, 37(11):1264-1269.

[99]OkazakiF, MatsunagaN, OkazakiH, et al., 2010. Circadian rhythm of transferrin receptor 1 gene expression controlled by c-Myc in colon cancer-bearing mice. Cancer Res, 70(15):6238-6246.

[100]OsborneNJ, GurrinLC, AllenKJ, et al., 2010. HFE C282Y homozygotes are at increased risk of breast and colorectal cancer. Hepatology, 51(4):1311-1318.

[101]ParkerJL, DemeJC, KolokourisD, et al., 2021. Molecular basis for redox control by the human cystine/glutamate antiporter system xc^-. Nat Commun, 12:7147.

[102]PasrichaSR, Tye-DinJ, MuckenthalerMU, et al., 2021. Iron deficiency. Lancet, 397(10270):233-248.

[103]PatraS, BarondeauDP, 2019. Mechanism of activation of the human cysteine desulfurase complex by frataxin. Proc Natl Acad Sci USA, 116(39):19421-19430.

[104]PinnixZK, MillerLD, WangW, et al., 2010. Ferroportin and iron regulation in breast cancer progression and prognosis. Sci Transl Med, 2(43):43ra56.

[105]PoliM, AspertiM, RuzzenentiP, et al., 2014. Hepcidin antagonists for potential treatments of disorders with hepcidin excess. Front Pharmacol, 5:86.

[106]QiWC, LiZH, XiaLJ, et al., 2019. LncRNA GABPB1-AS1 and GABPB1 regulate oxidative stress during erastin-induced ferroptosis in HepG2 hepatocellular carcinoma cells. Sci Rep, 9:16185.

[107]QinX, ZhangJ, WangB, et al., 2021. Ferritinophagy is involved in the zinc oxide nanoparticles-induced ferroptosis of vascular endothelial cells. Autophagy, 17(12):4266-4285.

[108]RadulescuS, BrookesMJ, SalgueiroP, et al., 2012. Luminal iron levels govern intestinal tumorigenesis after Apc loss in vivo. Cell Rep, 2(2):270-282.

[109]RinnJL, ChangHY, 2012. Genome regulation by long noncoding RNAs. Annu Rev Biochem, 81:145-166.

[110]RohJL, KimEH, JangH, et al., 2017. Nrf2 inhibition reverses the resistance of cisplatin-resistant head and neck cancer cells to artesunate-induced ferroptosis. Redox Biol, 11:254-262.

[111]RouaultTA, 2013. Iron metabolism in the CNS: implications for neurodegenerative diseases. Nat Rev Neurosci, 14(8):551-564.

[112]SalahudeenAA, ThompsonJW, RuizJC, et al., 2009. An E3 ligase possessing an iron-responsive hemerythrin domain is a regulator of iron homeostasis. Science, 326(5953):722-726.

[113]SangLJ, JuHQ, LiuGP, et al., 2018. LncRNA CamK-A regulates Ca²⁺-signaling-mediated tumor microenvironment remodeling. Mol Cell, 72(1):71-83.e7.

[114]SangLJ, JuHQ, YangZZ, et al., 2021. Mitochondrial long non-coding RNA GAS5 tunes TCA metabolism in response to nutrient stress. Nat Metab, 3(1):90-106.

[115]SankaranVG, UlirschJC, TchaikovskiiV, et al., 2015. X-linked macrocytic dyserythropoietic anemia in females with an ALAS2 mutation. J Clin Invest, 125(4):1665-1669.

[116]SaxenaN, MaioN, CrooksDR, et al., 2016. SDHB-deficient cancers: the role of mutations that impair iron sulfur cluster delivery. J Natl Cancer Inst, 108(1):djv287.

[117]SchmittAM, ChangHY, 2016. Long noncoding RNAs in cancer pathways. Cancer Cell, 29(4):452-463.

[118]SchonbergDL, MillerTE, WuQL, et al., 2015. Preferential iron trafficking characterizes glioblastoma stem-like cells. Cancer Cell, 28(4):441-455.

[119]ShawGC, CopeJJ, LiLT, et al., 2006. Mitoferrin is essential for erythroid iron assimilation. Nature, 440(7080):96-100.

[120]ShiH, GuYC, YangJ, et al., 2008. Lipocalin 2 promotes lung metastasis of murine breast cancer cells. J Exp Clin Cancer Res, 27:83.

[121]ShiQF, LiYD, LiSY, et al., 2020. LncRNA DILA1 inhibits Cyclin D1 degradation and contributes to tamoxifen resistance in breast cancer. Nat Commun, 11:5513.

[122]ShimizuT, LengalovaA, MartínekV, et al., 2019. Heme: emergent roles of heme in signal transduction, functional regulation and as catalytic centres. Chem Soc Rev, 48(24):5624-5657.

[123]StehlingO, VashishtAA, MascarenhasJ, et al., 2012. MMS19 assembles iron-sulfur proteins required for DNA metabolism and genomic integrity. Science, 337(6091):195-199.

[124]StehlingO, MascarenhasJ, VashishtAA, et al., 2013. Human CIA2A-FAM96A and CIA2B-FAM96B integrate iron homeostasis and maturation of different subsets of cytosolic-nuclear iron-sulfur proteins. Cell Metab, 18(2):187-198.

[125]StockwellBR, Friedmann AngeliJP, BayirH, et al., 2017. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell, 171(2):273-285.

[126]StockwellBR, JiangXJ, GuW, 2020. Emerging mechanisms and disease relevance of ferroptosis. Trends Cell Biol, 30(6):478-490.

[127]SunH, HuangZH, ShengWQ, et al., 2018. Emerging roles of long non-coding RNAs in tumor metabolism. J Hematol Oncol, 11:106.

[128]SunM, NieFQ, WangYF, et al., 2016. LncRNA HOXA11-AS promotes proliferation and invasion of gastric cancer by scaffolding the chromatin modification factors PRC2, LSD1, and DNMT1. Cancer Res, 76(21):6299-6310.

[129]TanYT, LinJF, LiT, et al., 2021. LncRNA-mediated posttranslational modifications and reprogramming of energy metabolism in cancer. Cancer Commun (Lond), 41(2):109-120.

[130]TangZ, JiangWL, MaoM, et al., 2021. Deubiquitinase USP35 modulates ferroptosis in lung cancer via targeting ferroportin. Clin Transl Med, 11(4):e390.

[131]TarínC, Fernandez-GarciaCE, BurilloE, et al., 2016. Lipocalin-2 deficiency or blockade protects against aortic abdominal aneurysm development in mice. Cardiovasc Res, 111(3):262-273.

[132]TesfayL, ClausenKA, KimJW, et al., 2015. Hepcidin regulation in prostate and its disruption in prostate cancer. Cancer Res, 75(11):2254-2263.

[133]To-FiguerasJ, DucampS, ClaytonJ, et al., 2011. ALAS2 acts as a modifier gene in patients with congenital erythropoietic porphyria. Blood, 118(6):1443-1451.

[134]TongWH, SourbierC, KovtunovychG, et al., 2011. The glycolytic shift in fumarate-hydratase-deficient kidney cancer lowers AMPK levels, increases anabolic propensities and lowers cellular iron levels. Cancer Cell, 20(3):315-327.

[135]TortiSV, TortiFM, 2013. Iron and cancer: more ore to be mined. Nat Rev Cancer, 13(5):342-355.

[136]VelaD, Vela-GaxhaZ, 2018. Differential regulation of hepcidin in cancer and non-cancer tissues and its clinical implications. Exp Mol Med, 50(2):e436.

[137]ViswanathanVS, RyanMJ, DhruvHD, et al., 2017. Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway. Nature, 547(7664):453-457.

[138]WangB, TontonozP, 2019. Phospholipid remodeling in physiology and disease. Annu Rev Physiol, 81:165-188.

[139]WangB, ZhangJQ, SongF, et al., 2016. EGFR regulates iron homeostasis to promote cancer growth through redistribution of transferrin receptor 1. Cancer Lett, 381(2):331-340.

[140]WangCQ, LiYM, YanS, et al., 2020. Interactome analysis reveals that lncRNA HULC promotes aerobic glycolysis through LDHA and PKM2. Nat Commun, 11:3162.

[141]WangJF, WangC, XuP, et al., 2021. PRMT1 is a novel molecular therapeutic target for clear cell renal cell carcinoma. Theranostics, 11(11):5387-5403.

[142]WangKC, ChangHY, 2011. Molecular mechanisms of long noncoding RNAs. Mol Cell, 43(6):904-914.

[143]WangLY, LiuYC, DuTT, et al., 2020. ATF3 promotes erastin-induced ferroptosis by suppressing system Xc^-. Cell Death Differ, 27(2):662-675.

[144]WangM, MaoC, OuyangLL, et al., 2019. Long noncoding RNA LINC00336 inhibits ferroptosis in lung cancer by functioning as a competing endogenous RNA. Cell Death Differ, 26(11):2329-2343.

[145]WangW, DengZY, HatcherH, et al., 2014. IRP2 regulates breast tumor growth. Cancer Res, 74(2):497-507.

[146]WangYF, YuL, DingJ, et al., 2018. Iron metabolism in cancer. Int J Mol Sci, 20(1):95.

[147]WangZL, ChenXW, LiuN, et al., 2021. A nuclear long non-coding RNA LINC00618 accelerates ferroptosis in a manner dependent upon apoptosis. Mol Ther, 29(1):263-274.

[148]WeiS, QiuTM, YaoXF, et al., 2020. Arsenic induces pancreatic dysfunction and ferroptosis via mitochondrial ROS-autophagy-lysosomal pathway. J Hazard Mater, 384:121390.

[149]WuCK, DaileyHA, RoseJP, et al., 2001. The 2.0 Å structure of human ferrochelatase, the terminal enzyme of heme biosynthesis. Nat Struct Biol, 8(2):156-160.

[150]WuJ, MinikesAM, GaoMH, et al., 2019. Intercellular interaction dictates cancer cell ferroptosis via NF2-YAP signalling. Nature, 572(7769):402-406.

[151]WuKJ, PolackA, Dalla-FaveraR, 1999. Coordinated regulation of iron-controlling genes, H-ferritin and IRP2, by c-MYC. Science, 283(5402):676-679.

[152]WuYQ, ZhangSW, GongXX, et al., 2020. The epigenetic regulators and metabolic changes in ferroptosis-associated cancer progression. Mol Cancer, 19:39.

[153]WuYY, JiangJN, FangXD, et al., 2018. STEAP1 regulates tumorigenesis and chemoresistance during peritoneal metastasis of gastric cancer. Front Physiol, 9:1132.

[154]XiaoX, YeohBS, Vijay-KumarM, 2017. Lipocalin 2: an emerging player in iron homeostasis and inflammation. Annu Rev Nutr, 37:103-130.

[155]XieY, HouW, SongX, et al., 2016. Ferroptosis: process and function. Cell Death Differ, 23(3):369-379.

[156]XuHN, JiangY, XuXQ, et al., 2019. Inducible degradation of lncRNA Sros1 promotes IFN-γ-mediated activation of innate immune responses by stabilizing Stat1 mRNA. Nat Immunol, 20(12):1621-1630.

[157]XuJ, WuKJ, JiaQJ, et al., 2020. Roles of miRNA and lncRNA in triple-negative breast cancer. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 21(9):673-689.

[158]XueX, TaylorM, AndersonE, et al., 2012. Hypoxia-inducible factor-2α activation promotes colorectal cancer progression by dysregulating iron homeostasis. Cancer Res, 72(9):2285-2293.

[159]XueX, RamakrishnanSK, WeiszK, et al., 2016. Iron uptake via DMT1 integrates cell cycle with JAK-STAT3 signaling to promote colorectal tumorigenesis. Cell Metab, 24(3):447-461.

[160]XueX, BredellBX, AndersonER, et al., 2017. Quantitative proteomics identifies STEAP4 as a critical regulator of mitochondrial dysfunction linking inflammation and colon cancer. Proc Natl Acad Sci USA, 114(45):E9608-E9617.

[161]YamazakiT, SouquereS, ChujoT, et al., 2018. Functional domains of NEAT1 architectural lncRNA induce paraspeckle assembly through phase separation. Mol Cell, 70(6):1038-1053.e7.

[162]YangWS, StockwellBR, 2016. Ferroptosis: death by lipid peroxidation. Trends Cell Biol, 26(3):165-176.

[163]YangWS, SriramaratnamR, WelschME, et al., 2014. Regulation of ferroptotic cancer cell death by GPX4. Cell, 156(1-2):317-331.

[164]YuanP, QiXY, SongAP, et al., 2021. LncRNA MAYA promotes iron overload and hepatocyte senescence through inhibition of YAP in non-alcoholic fatty liver disease. J Cell Mol Med, 25(15):7354-7366.

[165]ZhangCG, ZhangF, 2015. Iron homeostasis and tumorigenesis: molecular mechanisms and therapeutic opportunities. Protein Cell, 6(2):88-100.

[166]ZhangKM, PingLQ, DuT, et al., 2021. A ferroptosis-related lncRNAs signature predicts prognosis and immune microenvironment for breast cancer. Front Mol Biosci, 8:678877.

[167]ZhangYL, ShiJJ, LiuXG, et al., 2018. BAP1 links metabolic regulation of ferroptosis to tumour suppression. Nat Cell Biol, 20(10):1181-1192.

[168]ZhangYY, GuoSQ, WangS, et al., 2021. LncRNA OIP5-AS1 inhibits ferroptosis in prostate cancer with long-term cadmium exposure through miR-128-3p/SLC7A11 signaling. Ecotoxicol Environ Saf, 220:112376.

[169]ZhaoMM, WangRS, ZhouYL, et al., 2020. Emerging relationship between RNA helicases and autophagy. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 21(10):767-778.

[170]ZhengX, HanH, LiuGP, et al., 2017. LncRNA wires up Hippo and Hedgehog signaling to reprogramme glucose metabolism. EMBO J, 36(22):3325-3335.

[171]ZhengZY, ZhangQ, WuW, et al., 2021. Identification and validation of a ferroptosis-related long non-coding RNA signature for predicting the outcome of lung adenocarcinoma. Front Genet, 12:690509.

[172]ZhouBR, LiuJ, KangR, et al., 2020. Ferroptosis is a type of autophagy-dependent cell death. Semin Cancer Biol, 66:89-100.