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Ferroptosis: opening up potential targets for gastric cancer treatment

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Abstract

The fifth most frequent cancer in the world is gastric cancer. It ranks as the fourth most common reason for cancer-related deaths. Even though surgery is the only curative treatment for stomach cancer, adding adjuvant radiotherapy and chemotherapy is preferable than only surgery. The majority of patients, however, are discovered to be extremely tardy the first time and have a terrible prognosis. Therefore, it is necessary to create more viable therapy modalities. A growing number of studies in recent years have shown that ferroptosis and many cancer types are related. This gives our treatment a fresh viewpoint. We investigated the relationship between different signal pathways and non-coding RNA on ferroptosis in gastric cancer cells. Also discussed the targets cause ferroptosis resistance increased or reduced to the influence of the chemoresistance,proliferation and metastasis.

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References

  1. Machlowska J, Baj J, Sitarz M, Maciejewski R, Sitarz R (2020) Gastric cancer: epidemiology, risk factors, classification, genomic characteristics and treatment strategies. Int J Mol Sci 21(11):4012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Thrift AP, El-Serag HB (2020) Burden of gastric cancer. Clin Gastroenterol Hepatol 18(3):534–542

    Article  PubMed  Google Scholar 

  3. Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE et al (2012) Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149(5):1060–1072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Wang Y, Wei Z, Pan K, Li J, Chen Q (2020) The function and mechanism of ferroptosis in cancer. Apoptosis 25(11–12):786–798

    Article  CAS  PubMed  Google Scholar 

  5. Grady WM, Yu M, Markowitz SD (2021) Epigenetic Alterations in the gastrointestinal tract: current and emerging use for biomarkers of cancer. Gastroenterology 160(3):690–709

    Article  CAS  PubMed  Google Scholar 

  6. Han C, Liu Y, Dai R, Ismail N, Su W, Li B (2020) Ferroptosis and its potential role in human diseases. Front Pharmacol 11:239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Wang H, Liu C, Zhao Y, Gao G (2020) Mitochondria regulation in ferroptosis. Eur J Cell Biol 99(1):151058

    Article  CAS  PubMed  Google Scholar 

  8. Friedmann Angeli JP, Schneider M, Proneth B, Tyurina YY, Tyurin VA, Hammond VJ et al (2014) Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat Cell Biol 16(12):1180–1191

    Article  CAS  PubMed  Google Scholar 

  9. Battaglia AM, Chirillo R, Aversa I, Sacco A, Costanzo F, Biamonte F (2020) Ferroptosis and cancer: mitochondria meet the “Iron Maiden” Cell death. Cells 9(6):1505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Xie Y, Hou W, Song X, Yu Y, Huang J, Sun X et al (2016) Ferroptosis: process and function. Cell Death Differ 23(3):369–379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lewerenz J, Hewett SJ, Huang Y, Lambros M, Gout PW, Kalivas PW et al (2013) The cystine/glutamate antiporter system x(c)(-) in health and disease: from molecular mechanisms to novel therapeutic opportunities. Antioxid Redox Signal 18(5):522–555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Bannai S (1986) Exchange of cystine and glutamate across plasma membrane of human fibroblasts. J Biol Chem 261(5):2256–2263

    Article  CAS  PubMed  Google Scholar 

  13. Maiorino M, Conrad M, Ursini F (2018) GPx4, lipid peroxidation, and cell death: discoveries, rediscoveries, and open issues. Antioxid Redox Signal 29(1):61–74

    Article  CAS  PubMed  Google Scholar 

  14. Yang Y, Luo M, Zhang K, Zhang J, Gao T, Connell DO et al (2020) Nedd4 ubiquitylates VDAC2/3 to suppress erastin-induced ferroptosis in melanoma. Nat Commun 11(1):433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Li J, Cao F, Yin HL, Huang ZJ, Lin ZT, Mao N et al (2020) Ferroptosis: past, present and future. Cell Death Dis 11(2):88

    Article  PubMed  PubMed Central  Google Scholar 

  16. Ursini F, Maiorino M (2020) Lipid peroxidation and ferroptosis: the role of GSH and GPx4. Free Radical Biol Med 152:175–185

    Article  CAS  Google Scholar 

  17. Goldstein JL, Brown MS (1990) Regulation of the mevalonate pathway. Nature 343(6257):425–430

    Article  CAS  PubMed  Google Scholar 

  18. Bersuker K, Hendricks JM, Li Z, Magtanong L, Ford B, Tang PH et al (2019) The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature 575(7784):688–692

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Doll S, Freitas FP, Shah R, Aldrovandi M, da Silva MC, Ingold I et al (2019) FSP1 is a glutathione-independent ferroptosis suppressor. Nature 575(7784):693–698

    Article  CAS  PubMed  Google Scholar 

  20. Kagan VE, Mao G, Qu F, Angeli JP, Doll S, Croix CS et al (2017) Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis. Nat Chem Biol 13(1):81–90

    Article  CAS  PubMed  Google Scholar 

  21. Richard D, Kefi K, Barbe U, Bausero P, Visioli F (2008) Polyunsaturated fatty acids as antioxidants. Pharmacol Res 57(6):451–455

    Article  CAS  PubMed  Google Scholar 

  22. Küch EM, Vellaramkalayil R, Zhang I, Lehnen D, Brügger B, Sreemmel W et al (2014) Differentially localized acyl-CoA synthetase 4 isoenzymes mediate the metabolic channeling of fatty acids towards phosphatidylinositol. Biochem Biophys Acta 1841(2):227–239

    PubMed  Google Scholar 

  23. Dixon SJ, Winter GE, Musavi LS, Lee ED, Snijder B, Rebsamen M et al (2015) Human Haploid cell genetics reveals roles for lipid metabolism genes in nonapoptotic cell death. ACS Chem Biol 10(7):1604–1609

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Doll S, Proneth B, Tyurina YY, Panzilius E, Kobayashi S, Ingold I et al (2017) ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat Chem Biol 13(1):91–98

    Article  CAS  PubMed  Google Scholar 

  25. Shindou H, Shimizu T (2009) Acyl-CoA:lysophospholipid acyltransferases. J Biol Chem 284(1):1–5

    Article  CAS  PubMed  Google Scholar 

  26. Shintoku R, Takigawa Y, Yamada K, Kubota C, Yoshimoto Y, Takeuchi T et al (2017) Lipoxygenase-mediated generation of lipid peroxides enhances ferroptosis induced by erastin and RSL3. Cancer Sci 108(11):2187–2194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Yuan H, Li X, Zhang X, Kang R, Tang D (2016) Identification of ACSL4 as a biomarker and contributor of ferroptosis. Biochem Biophys Res Commun 478(3):1338–1343

    Article  CAS  PubMed  Google Scholar 

  28. Magtanong L, Ko PJ, To M, Cao JY, Forcina GC, Tarangelo A et al (2019) Exogenous monounsaturated fatty acids promote a ferroptosis-resistant cell state. Cell Chem Biol 26(3):420–32.e9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Henning Y, Blind US, Larafa S, Matschke J, Fandrey J (2022) Hypoxia aggravates ferroptosis in RPE cells by promoting the Fenton reaction. Cell Death Dis 13(7):662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Pantopoulos K, Porwal SK, Tartakoff A, Devireddy L (2012) Mechanisms of mammalian iron homeostasis. Biochemistry 51(29):5705–5724

    Article  CAS  PubMed  Google Scholar 

  31. Kawabata H (2019) Transferrin and transferrin receptors update. Free Radical Biol Med 133:46–54

    Article  CAS  Google Scholar 

  32. Hadian K, Stockwell BR (2020) SnapShot: ferroptosis. Cell 181(5):1188-e1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wu L, Tian X, Zuo H, Zheng W, Li X, Yuan M et al (2022) miR-124-3p delivered by exosomes from heme oxygenase-1 modified bone marrow mesenchymal stem cells inhibits ferroptosis to attenuate ischemia-reperfusion injury in steatotic grafts. J Nanobiotechnol 20(1):196

    Article  CAS  Google Scholar 

  34. Torii S, Shintoku R, Kubota C, Yaegashi M, Torii R, Sasaki M et al (2016) An essential role for functional lysosomes in ferroptosis of cancer cells. Biochem J 473(6):769–777

    Article  CAS  PubMed  Google Scholar 

  35. Pastushenko I, Blanpain C (2019) EMT Transition states during tumor progression and metastasis. Trends Cell Biol 29(3):212–226

    Article  CAS  PubMed  Google Scholar 

  36. Radisky DC, Levy DD, Littlepage LE, Liu H, Nelson CM, Fata JE et al (2005) Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature 436(7047):123–127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Liu RM, Vayalil PK, Ballinger C, Dickinson DA, Huang WT, Wang S et al (2012) Transforming growth factor β suppresses glutamate-cysteine ligase gene expression and induces oxidative stress in a lung fibrosis model. Free Radical Biol Med 53(3):554–563

    Article  CAS  Google Scholar 

  38. Hayes JD, Dinkova-Kostova AT, Tew KD (2020) Oxidative stress in cancer. Cancer Cell 38(2):167–197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kamada T, Maruyama Y, Monobe Y, Haruma K (2022) Endoscopic features and clinical importance of autoimmune gastritis. Dig Endosc 34(4):700–713

    Article  PubMed  Google Scholar 

  40. Yang J, Wei H, Liu M, Huang T, Fang X, Ren X et al (2022) Prognostic biomarker HAMP and associates with immune infiltration in gastric cancer. Int Immunopharmacol 108:108839

    Article  CAS  PubMed  Google Scholar 

  41. Noto JM, Piazuelo MB, Shah SC, Romero-Gallo J, Hart JL, Di C et al (2022) Iron deficiency linked to altered bile acid metabolism promotes Helicobacter pylori-induced inflammation-driven gastric carcinogenesis. J Clin Invest. https://doi.org/10.1172/JCI147822

    Article  PubMed  PubMed Central  Google Scholar 

  42. Yang WS, SriRamaratnam R, Welsch ME, Shimada K, Skouta R, Viswanathan VS et al (2014) Regulation of ferroptotic cancer cell death by GPX4. Cell 156(1–2):317–331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Zhu W, Liu D, Lu Y, Sun J, Zhu J, Xing Y et al (2023) PHKG2 regulates RSL3-induced ferroptosis in Helicobacter pylori related gastric cancer. Arch Biochem Biophys 740:109560

    Article  CAS  PubMed  Google Scholar 

  44. Kirtonia A, Sethi G, Garg M (2020) The multifaceted role of reactive oxygen species in tumorigenesis. Cell Mol Life Sci 77(22):4459–4483

    Article  CAS  PubMed  Google Scholar 

  45. Xiao S, Liu X, Yuan L, Chen X, Wang F (2021) Expression of ferroptosis-related genes shapes tumor microenvironment and pharmacological profile in gastric cancer. Front Cell Dev Biol 9:694003

    Article  PubMed  PubMed Central  Google Scholar 

  46. Yao F, Zhan Y, Pu Z, Lu Y, Chen J, Deng J et al (2021) LncRNAs target ferroptosis-related genes and impair activation of CD4(+) T cell in gastric cancer. Front Cell Dev Biol 9:797339

    Article  PubMed  PubMed Central  Google Scholar 

  47. Yang M, Wu X, Hu J, Wang Y, Wang Y, Zhang L et al (2022) COMMD10 inhibits HIF1α/CP loop to enhance ferroptosis and radiosensitivity by disrupting Cu-Fe balance in hepatocellular carcinoma. J Hepatol 76(5):1138–1150

    Article  CAS  PubMed  Google Scholar 

  48. Jiang L, Kon N, Li T, Wang SJ, Su T, Hibshoosh H et al (2015) Ferroptosis as a p53-mediated activity during tumour suppression. Nature 520(7545):57–62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Guan Z, Chen J, Li X, Dong N (2020) Tanshinone IIA induces ferroptosis in gastric cancer cells through p53-mediated SLC7A11 down-regulation. Biosci Rep. https://doi.org/10.1042/BSR20201807

  50. Zhao H, Ding Y, Zhang L (2023) SIRT1/APE1 promotes the viability of gastric cancer cells by inhibiting p53 to suppress ferroptosis. Open Med (Wars) 18(1):20220620

    Article  CAS  PubMed  Google Scholar 

  51. Zhang J, Gao M, Niu Y, Sun J (2022) Identification of a novel ferroptosis inducer for gastric cancer treatment using drug repurposing strategy. Front Mol Biosci 9:860525

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Fu H, Zhang Z, Li D, Lv Q, Chen S, Zhang Z et al (2022) LncRNA PELATON, a ferroptosis suppressor and prognositic signature for GBM. Front Oncol 12:817737

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Yi J, Zhu J, Wu J, Thompson CB, Jiang X (2020) Oncogenic activation of PI3K-AKT-mTOR signaling suppresses ferroptosis via SREBP-mediated lipogenesis. Proc Natl Acad Sci USA 117(49):31189–31197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Hayes JD, Dinkova-Kostova AT (2014) The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends Biochem Sci 39(4):199–218

    Article  CAS  PubMed  Google Scholar 

  55. He F, Antonucci L, Karin M (2020) NRF2 as a regulator of cell metabolism and inflammation in cancer. Carcinogenesis 41(4):405–416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Wong EW, Chang F et al (2007) Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochem Biophys Acta 1773(8):1263–1284

    Article  CAS  PubMed  Google Scholar 

  57. Hu XF, Yao J, Gao SG, Wang XS, Peng XQ, Yang YT et al (2013) Nrf2 overexpression predicts prognosis and 5-FU resistance in gastric cancer. Asian Pac J Cancer Prev 14(9):5231–5235

    Article  PubMed  Google Scholar 

  58. Fu D, Wang C, Yu L, Yu R (2021) Induction of ferroptosis by ATF3 elevation alleviates cisplatin resistance in gastric cancer by restraining Nrf2/Keap1/xCT signaling. Cell Mol Biol Lett 26(1):26

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Wang T, Zhou Z, Wang C, Qin Y, Wu L, Hu B et al (2022) LTBP2 knockdown promotes ferroptosis in gastric cancer cells through p62-Keap1-Nrf2 pathway. Biomed Res Int 2022:6532253

    PubMed  PubMed Central  Google Scholar 

  60. Ma M, Kong P, Huang Y, Wang J, Liu X, Hu Y et al (2022) Activation of MAT2A-ACSL3 pathway protects cells from ferroptosis in gastric cancer. Free Radical Biol Med 181:288–299

    Article  CAS  Google Scholar 

  61. Ouyang S, Li H, Lou L, Huang Q, Zhang Z, Mo J et al (2022) Inhibition of STAT3-ferroptosis negative regulatory axis suppresses tumor growth and alleviates chemoresistance in gastric cancer. Redox Biol 52:102317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Mirzaei S, Saghari S, Bassiri F, Raesi R, Zarrabi A, Hushmandi K et al (2022) NF-κB as a regulator of cancer metastasis and therapy response: a focus on epithelial-mesenchymal transition. J Cell Physiol 237(7):2770–2795

    Article  CAS  PubMed  Google Scholar 

  63. Gambhir S, Vyas D, Hollis M, Aekka A, Vyas A (2015) Nuclear factor kappa B role in inflammation associated gastrointestinal malignancies. World J Gastroenterol 21(11):3174–3183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Echizen K, Horiuchi K, Aoki Y, Yamada Y, Minamoto T, Oshima H et al (2019) NF-κB-induced NOX1 activation promotes gastric tumorigenesis through the expansion of SOX2-positive epithelial cells. Oncogene 38(22):4250–4263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Yao F, Deng Y, Zhao Y, Mei Y, Zhang Y, Liu X et al (2021) A targetable LIFR-NF-κB-LCN2 axis controls liver tumorigenesis and vulnerability to ferroptosis. Nat Commun 12(1):7333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Li S, He Y, Chen K, Sun J, Zhang L, He Y et al (2021) RSL3 drives ferroptosis through NF-κB pathway activation and GPX4 depletion in glioblastoma. Oxid Med Cell Longev 2021:2915019

    Article  PubMed  PubMed Central  Google Scholar 

  67. Chen BL, Yu J, Zeng ZR, Chu WK, Wong CY, Cheng YY et al (2008) Rosiglitazone suppresses gastric carcinogenesis by up-regulating HCaRG expression. Oncol Rep 20(5):1093–1097

    CAS  PubMed  Google Scholar 

  68. Cao S, Fu B, Cai J, Zhang D, Wang C, Wu H (2022) Linc00852 from cisplatin-resistant gastric cancer cell-derived exosomes regulates COMMD7 to promote cisplatin resistance of recipient cells through microRNA-514a-5p. Cell Biol Toxicol. https://doi.org/10.1007/s10565-021-09685-y

    Article  PubMed  Google Scholar 

  69. Blanchet A, Bourgmayer A, Kurtz JE, Mellitzer G, Gaiddon C (2021) Isoforms of the p53 family and gastric cancer: a Ménage à Trois for an unfinished affair. Cancers (Basel) 13(4):916

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Qiu J, Sun M, Wang Y, Chen B (2020) Identification and validation of an individualized autophagy-clinical prognostic index in gastric cancer patients. Cancer Cell Int 20:178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Ingaramo MC, Sánchez JA, Dekanty A (2018) Regulation and function of p53: a perspective from Drosophila studies. Mech Dev 154:82–90

    Article  CAS  PubMed  Google Scholar 

  72. Liu H, Liu N, Zhao Y, Zhu X, Wang C, Liu Q et al (2019) Oncogenic USP22 supports gastric cancer growth and metastasis by activating c-Myc/NAMPT/SIRT1-dependent FOXO1 and YAP signaling. Aging (Albany NY) 11(21):9643–9660

    Article  CAS  PubMed  Google Scholar 

  73. Zhang W, Liao K, Liu D (2020) MiRNA-12129 Suppresses cell proliferation and block cell cycle progression by targeting SIRT1 in GASTRIC cancer. Technol Cancer Res Treat 19:1533033820928144

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Qiu G, Li X, Che X, Wei C, He S, Lu J et al (2015) SIRT1 is a regulator of autophagy: Implications in gastric cancer progression and treatment. FEBS Lett 589(16):2034–2042

    Article  CAS  PubMed  Google Scholar 

  75. Sun P, Yu H, Zhang WQ, Hu M, Lv R (2012) Lentivirus-mediated siRNA targeting VEGF inhibits gastric cancer growth in vivo. Oncol Rep 28(5):1687–1692

    Article  CAS  PubMed  Google Scholar 

  76. Manoel-Caetano FS, Rossi AFT, Calvet de Morais G, Severino FE, Silva AE (2019) Upregulation of the APE1 and H2AX genes and miRNAs involved in DNA damage response and repair in gastric cancer. Genes Dis 6(2):176–84

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Guo N, Chen Y, Zhang Y, Deng Y, Zeng F, Li X (2022) Potential role of APEX1 during ferroptosis. Front Oncol 12:798304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Lissabet JFB, Herrera Belén L, Lee-Estevez M, Risopatrón J, Valdebenito I, Figueroa E et al (2020) The CatSper channel is present and plays a key role in sperm motility of the Atlantic salmon (Salmo salar). Comp Biochem Physiol A Mol Integr Physiol 241:110634

    Article  CAS  PubMed  Google Scholar 

  79. Jiang L, Zhang M, Wang S, Xiao Y, Wu J, Zhou Y et al (2020) LINC01018 and SMIM25 sponged miR-182-5p in endometriosis revealed by the ceRNA network construction. Int J Immunopathol Pharmacol 34:2058738420976309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Sun Z, Dang Q, Liu Z, Shao B, Chen C, Guo Y et al (2021) LINC01272/miR-876/ITGB2 axis facilitates the metastasis of colorectal cancer via epithelial-mesenchymal transition. J Cancer 12(13):3909–3919

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Boudreau HE, Casterline BW, Burke DJ, Leto TL (2014) Wild-type and mutant p53 differentially regulate NADPH oxidase 4 in TGF-β-mediated migration of human lung and breast epithelial cells. Br J Cancer 110(10):2569–2582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Romeo MA, Gilardini Montani MS, Benedetti R, Arena A, D’Orazi G, Cirone M (2021) p53–R273H sustains ROS, Pro-inflammatory cytokine release and mTOR Activation while reducing autophagy, mitophagy and UCP2 expression, effects prevented by wtp53. Biomolecules 11(3):344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Willems L, Tamburini J, Chapuis N, Lacombe C, Mayeux P, Bouscary D (2012) PI3K and mTOR signaling pathways in cancer: new data on targeted therapies. Curr Oncol Rep 14(2):129–138

    Article  CAS  PubMed  Google Scholar 

  84. Yuan R, Kay A, Berg WJ, Lebwohl D (2009) Targeting tumorigenesis: development and use of mTOR inhibitors in cancer therapy. J Hematol Oncol 2:45

    Article  PubMed  PubMed Central  Google Scholar 

  85. Hay N, Sonenberg N (2004) Upstream and downstream of mTOR. Genes Dev 18(16):1926–1945

    Article  CAS  PubMed  Google Scholar 

  86. Bu Z, Ji J (2013) Therapeutic implications of mTOR inhibitors in the treatment of gastric cancer. Curr Cancer Drug Targets 13(2):121–125

    Article  CAS  PubMed  Google Scholar 

  87. Ricoult SJ, Yecies JL, Ben-Sahra I, Manning BD (2016) Oncogenic PI3K and K-Ras stimulate de novo lipid synthesis through mTORC1 and SREBP. Oncogene 35(10):1250–1260

    Article  CAS  PubMed  Google Scholar 

  88. Yecies JL, Zhang HH, Menon S, Liu S, Yecies D, Lipovsky AI et al (2011) Akt stimulates hepatic SREBP1c and lipogenesis through parallel mTORC1-dependent and independent pathways. Cell Metab 14(1):21–32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Shimano H, Sato R (2017) SREBP-regulated lipid metabolism: convergent physiology—divergent pathophysiology. Nat Rev Endocrinol 13(12):710–730

    Article  CAS  PubMed  Google Scholar 

  90. Xiao S, Liu X, Yuan L, Wang F (2021) A ferroptosis-related lncRNAs signature predicts prognosis and therapeutic response of gastric cancer. Front Cell Dev Biol 9:736682

    Article  PubMed  PubMed Central  Google Scholar 

  91. Canning P, Sorrell FJ, Bullock AN (2015) Structural basis of Keap1 interactions with Nrf2. Free Radical Biol Med 88(Pt B):101–107

    Article  CAS  Google Scholar 

  92. Ku HC, Cheng CF (2020) Master Regulator activating transcription factor 3 (ATF3) in metabolic homeostasis and cancer. Front Endocrinol (Lausanne) 11:556

    Article  PubMed  Google Scholar 

  93. Guan D, Zhou W, Wei H, Wang T, Zheng K, Yang C et al (2022) Ferritinophagy-mediated ferroptosis and activation of keap1/Nrf2/HO-1 pathway were conducive to EMT inhibition of gastric cancer cells in action of 2,2′-Di-pyridineketone hydrazone dithiocarbamate butyric acid ester. Oxid Med Cell Longev 2022:3920664

    Article  PubMed  PubMed Central  Google Scholar 

  94. Doumpas N, Lampart F, Robinson MD, Lentini A, Nestor CE, Cantù C et al (2019) TCF/LEF dependent and independent transcriptional regulation of Wnt/β-catenin target genes. Embo J. https://doi.org/10.15252/embj.201798873

    Article  PubMed  Google Scholar 

  95. Boj SF, van Es JH, Huch M, Li VS, José A, Hatzis P et al (2012) Diabetes risk gene and Wnt effector Tcf7l2/TCF4 controls hepatic response to perinatal and adult metabolic demand. Cell 151(7):1595–1607

    Article  CAS  PubMed  Google Scholar 

  96. Wang Y, Zheng L, Shang W, Yang Z, Li T, Liu F et al (2022) Wnt/beta-catenin signaling confers ferroptosis resistance by targeting GPX4 in gastric cancer. Cell Death Differ 29(11):2190–2202

    Article  PubMed  PubMed Central  Google Scholar 

  97. Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C et al (1999) Stat3 as an oncogene. Cell 98(3):295–303

    Article  CAS  PubMed  Google Scholar 

  98. Judd LM, Bredin K, Kalantzis A, Jenkins BJ, Ernst M, Giraud AS (2006) STAT3 activation regulates growth, inflammation, and vascularization in a mouse model of gastric tumorigenesis. Gastroenterology 131(4):1073–1085

    Article  CAS  PubMed  Google Scholar 

  99. Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136(4):629–641

    Article  CAS  PubMed  Google Scholar 

  100. Wei L, Sun J, Zhang N, Zheng Y, Wang X, Lv L et al (2020) Noncoding RNAs in gastric cancer: implications for drug resistance. Mol Cancer 19(1):62

    Article  PubMed  PubMed Central  Google Scholar 

  101. Zhang Z, Qiu X, Yan Y, Liang Q, Cai Y, Peng B et al (2021) Evaluation of ferroptosis-related gene AKR1C1 as a Novel biomarker associated with the immune microenvironment and prognosis in breast cancer. Int J Gen Med 14:6189–6200

    Article  PubMed  PubMed Central  Google Scholar 

  102. Mao C, Wang X, Liu Y, Wang M, Yan B, Jiang Y et al (2018) A G3BP1-Interacting lncRNA promotes ferroptosis and apoptosis in cancer via nuclear sequestration of p53. Cancer Res 78(13):3484–3496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Yang H, Hu Y, Weng M, Liu X, Wan P, Hu Y et al (2022) Hypoxia inducible lncRNA-CBSLR modulates ferroptosis through m6A-YTHDF2-dependent modulation of CBS in gastric cancer. J Adv Res 37:91–106

    Article  CAS  PubMed  Google Scholar 

  104. Huang G, Xiang Z, Wu H, He Q, Dou R, Lin Z et al (2022) The lncRNA BDNF-AS/WDR5/FBXW7 axis mediates ferroptosis in gastric cancer peritoneal metastasis by regulating VDAC3 ubiquitination. Int J Biol Sci 18(4):1415–1433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Zhang H, Wang M, He Y, Deng T, Liu R, Wang W et al (2021) Chemotoxicity-induced exosomal lncFERO regulates ferroptosis and stemness in gastric cancer stem cells. Cell Death Dis 12(12):1116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Ni H, Qin H, Sun C, Liu Y, Ruan G, Guo Q et al (2021) MiR-375 reduces the stemness of gastric cancer cells through triggering ferroptosis. Stem Cell Res Ther 12(1):325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Zhang H, Deng T, Liu R, Ning T, Yang H, Liu D et al (2020) CAF secreted miR-522 suppresses ferroptosis and promotes acquired chemo-resistance in gastric cancer. Mol Cancer 19(1):43

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Mao SH, Zhu CH, Nie Y, Yu J, Wang L (2021) Levobupivacaine induces ferroptosis by miR-489-3p/SLC7A11 signaling in gastric cancer. Front Pharmacol 12:681338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Liu YP, Qiu ZZ, Li XH, Li EY (2021) Propofol induces ferroptosis and inhibits malignant phenotypes of gastric cancer cells by regulating miR-125b-5p/STAT3 axis. World J Gastrointest Oncol 13(12):2114–2128

    Article  PubMed  PubMed Central  Google Scholar 

  110. Jiang M, Mo R, Liu C, Wu H (2022) Circ_0000190 sponges miR-382–5p to suppress cell proliferation and motility and promote cell death by targeting ZNRF3 in gastric cancer. J Biochem. https://doi.org/10.1093/jb/mvac003

    Article  PubMed  Google Scholar 

  111. Shao CJ, Zhou HL, Gao XZ, Xu CF (2023) Downregulation of miR-221-3p promotes the ferroptosis in gastric cancer cells via upregulation of ATF3 to mediate the transcription inhibition of GPX4 and HRD1. Transl Oncol 32:101649

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Li C, Tian Y, Liang Y, Li Q (2020) Circ_0008035 contributes to cell proliferation and inhibits apoptosis and ferroptosis in gastric cancer via miR-599/EIF4A1 axis. Cancer Cell Int 20(1):84

    Article  PubMed  PubMed Central  Google Scholar 

  113. Qiao HP, Gao WS, Huo JX, Yang ZS (2013) Long non-coding RNA GAS5 functions as a tumor suppressor in renal cell carcinoma. Asian Pac J Cancer Prev 14(2):1077–1082

    Article  PubMed  Google Scholar 

  114. Liao K, Xu J, Yang W, You X, Zhong Q, Wang X (2018) The research progress of LncRNA involved in the regulation of inflammatory diseases. Mol Immunol 101:182–188

    Article  CAS  PubMed  Google Scholar 

  115. Yang Z, Jiang S, Shang J, Jiang Y, Dai Y, Xu B et al (2019) LncRNA: shedding light on mechanisms and opportunities in fibrosis and aging. Ageing Res Rev 52:17–31

    Article  CAS  PubMed  Google Scholar 

  116. Wei J, Zeng Y, Gao X, Liu T (2021) A novel ferroptosis-related lncRNA signature for prognosis prediction in gastric cancer. BMC Cancer 21(1):1221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Li R, Xiao C, Liu H, Huang Y, Dilger JP, Lin J (2018) Effects of local anesthetics on breast cancer cell viability and migration. BMC Cancer 18(1):666

    Article  PubMed  PubMed Central  Google Scholar 

  118. Huang W, Wu Y, Qiao M, Xie Z, Cen X, Huang X et al (2022) CircRNA-miRNA networks in regulating bone disease. J Cell Physiol 237(2):1225–1244

    Article  CAS  PubMed  Google Scholar 

  119. Li P, Chen S, Chen H, Mo X, Li T, Shao Y et al (2015) Using circular RNA as a novel type of biomarker in the screening of gastric cancer. Clin Chimica Acta Int J Clin Chem 444:132–6

    Article  CAS  Google Scholar 

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Funding

This work was supported by National key research and development project Sub-topics (NO.2021YE0192100), Natural Science Foundation of Hunan Province (NO.2023JJ30529 NO.2020JJ4083), Key Projects of Hunan Provincial Education Department (NO. 21A0285).

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Authors and Affiliations

  1. Key Laboratory of Cancer Cellular and Molecular Pathology in Hunan Province, Cancer Research Institute of Hengyang Medical College, University of South China, 28 Changsheng Road, Hengyang, 421001, Hunan, China

    Yuwei Li, Jiangrong Liu & Zhiwei Zhang

  2. Department of Pathology, The Second Affiliated Hospital, Shaoyang University, Shaoyang, 422000, Hunan, China

    Shihua Wu

  3. Department of Head and Neck Surgery, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China

    Juan Xiao

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  1. Yuwei Li
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  2. Jiangrong Liu
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  3. Shihua Wu
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  4. Juan Xiao
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  5. Zhiwei Zhang
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Contributions

YL, JL wrote the manuscript and drew the figures; JX, SW collected literature; JX, ZZ supervised the work.

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Correspondence to Juan Xiao or Zhiwei Zhang.

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Li, Y., Liu, J., Wu, S. et al. Ferroptosis: opening up potential targets for gastric cancer treatment. Mol Cell Biochem (2023). https://doi.org/10.1007/s11010-023-04886-x

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