Exosome-Mediated Ferroptosis Regulation in Gastric Cancer: Mechanisms, Challenges, and Therapeutic Potential

Authors

  • Zohreh Rezaei University of Sistan and Baluchestan Author
  • Farzad Sadri University of Sistan and Baluchestan Author

DOI:

https://doi.org/10.63623/fbzn4v28

Keywords:

Biomarker, Exosomes, Ferroptosis, Gastric Cancer, Non-Coding RNAs

Abstract

Gastric cancer (GC) persists as one of the foremost contributors to cancer-associated morbidity and mortality worldwide, with limited effective therapies for advanced disease stages. Recent progress in cancer biology has spotlighted ferroptosis__an iron-dependent, regulated mode of cell death__as a promising avenue for therapeutic intervention. Exosomes__small extracellular vesicles that mediate intercellular communication__have emerged as pivotal modulators of ferroptosis through the transfer of bioactive molecules such as lipids, proteins, and RNAs. In the context of GC, exosomes influence critical metabolic pathways including iron homeostasis, oxidative stress, and lipid peroxidation, thereby contributing to tumor progression, metastasis, and therapeutic resistance. This review endeavors to comprehensively elucidate the current understanding of exosome-mediated ferroptosis regulation in gastric cancer, delineate the underlying molecular mechanisms, and to assess their potential as novel diagnostic and therapeutic targets. The review further highlights existing knowledge gaps and suggests.

References

[1] Machlowska J, Baj J, Sitarz M, Maciejewski R, Sitarz R. Gastric cancer: Epidemiology, risk factors, classification, genomic characteristics and treatment strategies. International Journal of Molecular Sciences, 2020, 21(11), 4012. DOI: 10.3390/ijms21114012

[2] Lattanzi W, Ripoli C, Greco V, Barba M, Iavarone F, et al. Basic and preclinical research for personalized medicine. Journal of Personalized Medicine, 2021, 11(5), 354. DOI: 10.3390/jpm11050354

[3] Li C, Jiang P, Wei S, Xu X, Wang J. Regulatory T cells in tumor microenvironment: New mechanisms, potential therapeutic strategies and future prospects. Molecular Cancer, 2020, 19, 1-23. DOI: 10.1186/s12943-020-01234-1

[4] Johnstone RM, Adam M, Hammond J, Orr L, Turbide C. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). Journal of Biological Chemistry, 1987, 262(19), 9412-9420.

[5] Couch Y, Buzàs EI, Di Vizio D, Gho YS, Harrison P, et al. A brief history of nearly EV‐erything-The rise and rise of extracellular vesicles. Journal of Extracellular Vesicles, 2021, 10(14), e12144. DOI: 10.1002/jev2.12144

[6] Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, et al. Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell, 2012, 149(5), 1060-1072. DOI: 10.1016/j.cell.2012.03.042

[7] Chu B, Kon N, Chen D, Li T, Liu T, et al. ALOX12 is required for P53-mediated tumour suppression through a distinct ferroptosis pathway. Nature Cell Biology, 2019, 21(5), 579-591. DOI: 10.1038/s41556-019-0305-6

[8] Han C, Zhang C, Wang H, Zhao L. Exosome-mediated communication between tumor cells and tumor-associated macrophages: implications for tumor microenvironment. Oncoimmunology, 2021, 10(1), 1887552. DOI: 10.1080/2162402X.2021.1887552

[9] Yang P, Yang W, Wei Z, Li Y, Yang Y, et al. Novel targets for gastric cancer: The tumor microenvironment (TME), N6-Methyladenosine (m6A), pyroptosis, autophagy, ferroptosis and cuproptosis. Biomedicine & Pharmacotherapy, 2023, 163, 114883. DOI: 10.1016/j.biopha.2023.114883

[10]Le J, Pan G, Zhang C, Chen Y, Tiwari AK, et al. Targeting ferroptosis in gastric cancer: strategies and opportunities. Immunological Reviews, 2024, 321(1), 228-245. DOI: 10.1111/imr.13280

[11]Das A. Extracellular Vesicles: Tiny messengers for mighty rna delivery. Biologics, 2024, 4(1), 88-104. DOI: 10.3390/biologics4010007

[12]Wang J, Barr MM, Wehman AM. Extracellular vesicles. Genetics, 2024, 227(4), iyae088. DOI: 10.1093/genetics/iyae088

[13]Jahnke K, Staufer O. Membranes on the move: The functional role of the extracellular vesicle membrane for contact‐dependent cellular signalling. Journal of Extracellular Vesicles, 2024, 13(4), e12436. DOI: 10.1002/jev2.12436

[14]Rezaei Z, Rostami Ravari N, Sadri F, Mahdiabadi MA, Mohammadi Y, et al. Ferroptosis and noncoding RNAs: exploring mechanisms in lung cancer treatment. Frontiersin Cell and Developmental Biology, 2025, 13, 1522873. DOI: 10.3389/fcell.2025.1522873

[15]Chuang YT, Yen CY, Chien TM, Chang FR, Tsai YH, et al. Ferroptosis-regulated natural products and miRNAs and their potential targeting to ferroptosis and exosome biogenesis. International Journal of Molecular Sciences, 2024, 25(11), 6083. DOI: 10.3390/ijms25116083

[16]Zhang Y, Xie J. Unveiling the role of ferroptosis-associated exosomal non-coding RNAs in cancer pathogenesis. Biomedicine & Pharmacotherapy, 2024, 172, 116235. DOI: 10.1016/j.biopha.2024.116235

[17]Lee YJ, Shin KJ, Chae YC. Regulation of cargo selection in exosome biogenesis and its biomedical applications in cancer. Experimental and Molecular Medicine, 2024, 56(4), 877-889. DOI: 10.1038/s12276-024-01209-y

[18]Hurley JH. The ESCRT complexes. Critical Reviews In Biochemistry and Molecular Biology, 2010, 45(6), 463-487. DOI: 10.3109/10409238.2010.502516

[19]Hurley JH. ESCRT S are everywhere. The EMBO Journal, 2015, 34(19), 2398-2407. DOI: 10.15252/embj.201592484

[20]Henne WM, Buchkovich NJ, Emr SD. The ESCRT Pathway. Developmental Cell, 2011, 21(1), 77-91. DOI: 10.1016/j.devcel.2011.05.015

[21]Rink J, Ghigo E, Kalaidzidis Y, Zerial M. Rab conversion as a mechanism of progression from early to late endosomes. Cell, 2005, 122(5), 735-749. DOI: 10.1016/j.cell.2005.06.043

[22]Théry C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nature Reviews Immunology, 2009, 9(8), 581-593. DOI: 10.1038/nri2567

[23]Tang XH, Guo T, Gao XY, Wu XL, Xing XF, et al. Exosome-derived noncoding RNAs in gastric cancer: Functions and clinical applications. Molecular Cancer, 2021, 20(1), 99. DOI: 10.1186/s12943-021-01396-6

[24]Xu M, Ji J, Jin D, Wu Y, Wu T, et al. The biogenesis and secretion of exosomes and multivesicular bodies (MVBs): Intercellular shuttles and implications in human diseases. Genes & Diseases, 2023, 10(5), 1894-1907. DOI: 10.1016/j.gendis.2022.03.021

[25]Yeates EF, Tesco G. The endosome-associated deubiquitinating enzyme USP8 regulates BACE1 enzyme ubiquitination and degradation. Journal of Biological Chemistry, 2016, 291(30), 15753-15766. DOI: 10.1074/jbc.M116.718023

[26]Taylor DD, Gercel-Taylor C. The origin, function, and diagnostic potential of RNA within extracellular vesicles present in human biological fluids. Frontiers in Genetics, 2013, 4: 142. DOI: 10.3389/fgene.2013.00142

[27]Alberro A, Iparraguirre L, Fernandes A, Otaegui D. Extracellular vesicles in blood: Sources, effects, and applications. International Journal of Molecular Sciences, 2021, 22(15), 8163. DOI: 10.3390/ijms22158163

[28]Wei S, Peng L, Yang J, Sang H, Jin D, et al. Exosomal transfer of miR-15b-3p enhances tumorigenesis and malignant transformation through the DYNLT1/Caspase-3/Caspase-9 signaling pathway in gastric cancer. Journal of Experimental & Clinical Cancer Research, 2020, 39, 1-18. DOI: 10.1186/s13046-019-1511-6

[29]Peinado H, Lavotshkin S, Lyden D. The secreted factors responsible for pre-metastatic niche formation: Old sayings and new thoughts. Seminars In Cancer Biology, 2011, 21(2),139-146. DOI: 10.1016/j.semcancer.2011.01.002

[30]Di Bella MA. Overview and update on extracellular vesicles: Considerations on exosomes and their application in modern medicine. Biology (Basel), 2022, 11(6), 804. DOI: 10.3390/biology11060804

[31]Kowal J, Arras G, Colombo M, Jouve M, Morath JP, et al. Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proceedings of the National Academy of Sciences, 2016, 113(8), E968-E977. DOI: 10.1073/pnas.1521230113

[32]Wang T, Zhang H, Zhou Y, Shi J. Extrachromosomal circular DNA: A new potential role in cancer progression. Journal of Translational Medicine, 2021, 19(1), 257. DOI: 10.1186/s12967-021-02927-x

[33]Qiu GH, Fu M, Zheng X, Huang C. Protection of the genome and the central exome by peripheral non‐coding DNA against DNA Damage in health, ageing and age‐related diseases. Biological Reviews, 2024, 100(2), 508-529. DOI: 10.1111/brv.13151

[34]Wang X, Wang L, Lin H, Zhu Y, Huang D, et al. Research progress of CTC, ctDNA, and EVs in cancer liquid biopsy. Frontiers in Oncology, 2024, 14, 1303335. DOI: 10.3389/fonc.2024.1303335

[35]Deus CM, Tavares H, Beatriz M, Mota S, Lopes C. Mitochondrial damage-associated molecular patterns content in extracellular vesicles promotes early inflammation in neurodegenerative disorders. Cells, 2022, 11(15), 2364. DOI: 10.3390/cells11152364

[36]Quesenberry PJ, Aliotta J, Deregibus MC, Camussi G. Role of extracellular rna-carrying vesicles in cell differentiation and reprogramming. Stem Cell Research & Therapy , 2015, 6, 1-10. DOI: 10.1186/s13287-015-0150-x

[37]Cocks A, Martinez-Rodriguez V, Del Vecchio F, Schukking M, Broseghini E, et al. Diverse roles of EV-RNA in cancer progression. Seminars In Cancer Biology. 2021,75, 127-135. DOI: 10.1016/j.semcancer.2020.11.022

[38]O’Brien K, Breyne K, Ughetto S, Laurent LC, Breakefield XO. RNA delivery by extracellular vesicles in mammalian cells and its applications. Nature Reviews Molecular Cell Biology, 2020, 21(10), 585-606. DOI: 10.1038/s41580-020-0251-y

[39]Hu M, Li J, Liu C-G, Goh RMW, Yu F, et al. Noncoding RNAs of extracellular vesicles in tumor angiogenesis: From biological functions to clinical significance. Cells, 2022, 11(6), 947. DOI: 10.3390/cells11060947

[40]Romano R, Picca A, Eusebi LHU, Marzetti E, Calvani R, et al. Extracellular vesicles and pancreatic cancer: Insights on the roles of miRNA, lncRNA, and protein cargos in cancer progression. Cells, 2021, 10(6), 1361. DOI: 10.3390/cells10061361

[41]Ghadami S, Dellinger K. The lipid composition of extracellular vesicles: Applications in diagnostics and therapeutic delivery. Frontiers In Molecular Biosciences, 2023, 10, 1198044. DOI: 10.3389/fmolb.2023.1198044

[42]Hullin-Matsuda F, Colosetti P, Rabia M, Luquain-Costaz C, Delton I. Exosomal lipids from membrane organization to biomarkers: Focus on an endolysosomal-specific lipid. Biochimie, 2022, 203, 77-92. DOI: 10.1016/j.biochi.2022.09.016

[43]Lin Z, Hua G, Hu X. Lipid metabolism associated crosstalk: The bidirectional interaction between cancer cells and immune/stromal cells within the tumor microenvironment for prognostic insight. Cancer Cell International, 2024, 24(1), 295. DOI: 10.1186/s12935-024-03481-4

[44]Perez GI, Bernard MP, Vocelle D, Zarea AA, Saleh NA, et al. Phosphatidylserine-exposing Annexin A1-positive extracellular vesicles: Potential cancer biomarkers. Vaccines, 2023, 11(3), 639. DOI: 10.3390/vaccines11030639

[45]Vagner T, Chin A, Mariscal J, Bannykh S, Engman DM, et al. Protein composition reflects extracellular vesicle heterogeneity. Proteomics, 2019, 19(8), 1800167. DOI: 10.1002/pmic.201800167

[46]Nawaz M, Shah N, Zanetti BR, Maugeri M, Silvestre RN, et al. Extracellular vesicles and matrix remodeling enzymes: The emerging roles in extracellular matrix remodeling, progression of diseases and tissue repair. Cells, 2018, 7(10), 167. DOI: 10.3390/cells7100167

[47]Li XX, Yang LX, Wang C, Li H, Shi DS, et al. The roles of exosomal proteins: Classification, function, and applications. International Journal of Molecular Sciences, 2023, 24(4), 3061. DOI: 10.3390/ijms24043061

[48]Xu J, Liao K, Zhou W. Exosomes regulate the transformation of cancer cells in cancer stem cell homeostasis. Stem Cells International, 2018, 2018(1), 4837370. DOI: 10.1155/2018/4837370

[49]Lucchetti D, Ricciardi Tenore C, Colella F, Sgambato A. Extracellular vesicles and cancer: A focus on metabolism, cytokines, and immunity. Cancers, 2020, 12(1), 171. DOI: 10.3390/cancers12010171

[50]Zhao J, Zhang X, Li Y, Yu J, Chen Z, et al. Interorgan communication with the liver: Novel mechanisms and therapeutic targets. Frontiers in immunology, 2023, 14, 1314123. DOI: 10.3389/fimmu.2023.1314123

[51]Kumar MA, Baba SK, Sadida HQ, Marzooqi SA, Jerobin J, et al. Extracellular vesicles as tools and targets in therapy for diseases. Signal Transduction and Targeted Therapy, 2024, 9(1), 27. DOI: 10.1038/s41392-024-01735-1

[52]Theodoraki MN, Yerneni SS, Hoffmann TK, Gooding WE, Whiteside TL. Clinical significance of Pd-L1+ exosomes in plasma of head and neck cancer patients. Clinical Cancer Research, 2018, 24(4), 896-905. DOI: 10.1158/1078-0432.CCR-17-2664

[53]Yang Y, Li CW, Chan LC, Wei Y, Hsu JM, et al. Exosomal Pd-L1 harbors active defense function to suppress T cell killing of breast cancer cells and promote tumor growth. Cell Research, 2018, 28(8), 862-864. DOI: 10.1038/s41422-018-0060-4

[54]Cao JY, Dixon SJ. Mechanisms of ferroptosis. Cellular and Molecular Life Sciences, 2016, 73, 2195-2209. DOI: 10.1007/s00018-016-2194-1

[55]Wang B, Wang Y, Zhang J, Hu C, Jiang J, et al. ROS-induced lipid peroxidation modulates cell death outcome: Mechanisms behind apoptosis, autophagy, and ferroptosis. Archives of Toxicology, 2023, 97(6), 1439-1451. DOI: 10.1007/s00018-016-2194-1

[56]Hosseini SF, Javanshir-giv S, Soleimani H, Mollaei H, Sadri F, et al. The importance of hsa-miR-28 in human malignancies. Biomedicine & Pharmacotherapy, 2023, 161, 114453. DOI: 10.1016/j.biopha.2023.114453

[57]Do Q, Zhang R, Hooper G, Xu L. Differential contributions of distinct free radical peroxidation mechanisms to the induction of ferroptosis. Journal of the American Chemical Society, 2023, 3(4), 1100-1117. DOI: 10.1021/jacsau.2c00681

[58]Bayır H, Anthonymuthu TS, Tyurina YY, Patel SJ, Amoscato AA, et al. Achieving life through death: Redox biology of lipid peroxidation in ferroptosis. Cell Chemical Biology, 2020, 27(4), 387-408. DOI: 10.1016/j.chembiol.2020.03.014

[59]Venkataramani V. Iron homeostasis and metabolism: Two sides of a coin. Ferroptosis: Mechanism and Diseases, 2021, 25-40. DOI: 10.1007/978-3-030-62026-4_3

[60]Kouroumalis E, Tsomidis I, Voumvouraki A. Iron as a therapeutic target in chronic liver disease. World Journal of Gastroenterology, 2023, 29(4), 616. DOI: 10.3748/wjg.v29.i4.616

[61]Forcina GC, Dixon SJ. GPX4 at the crossroads of lipid homeostasis and ferroptosis. Proteomics, 2019, 19(18), 1800311. DOI: 10.1002/pmic.201800311

[62]Dar NJ, John U, Bano N, Khan S, Bhat SA. Oxytosis/ferroptosis in neurodegeneration: The underlying role of master regulator glutathione peroxidase 4 (GPX4). Molecular Neurobiology, 2024, 61(3), 1507-1526. DOI: 10.1007/s12035-023-03646-8

[63]Zhang C, Liu X, Jin S, Chen Y, Guo R. Ferroptosis in cancer therapy: A novel approach to reversing drug resistance. Molecular Cancer, 2022, 21(1), 47. DOI: 10.1186/s12943-022-01530-y

[64]Wu X, Iroegbu CD, Peng J, Guo J, Yang J, et al. Cell death and exosomes regulation after myocardial infarction and ischemia-reperfusion. Frontiersin Cell and Developmental Biology, 2021, 9, 673677. DOI: 10.3389/fcell.2021.673677

[65]Song Y, Wang B, Zhu X, Hu J, Sun J, et al. Human umbilical cord blood–derived mscs exosome attenuate myocardial injury by inhibiting ferroptosis in acute myocardial infarction mice. Cell Biology and Toxicology, 2021, 37(1), 51-64. DOI: 10.1007/s10565-020-09530-8

[66]Yi X, Tang X. Exosomes from miR-19b-3p-modified adscs inhibit ferroptosis in intracerebral hemorrhage mice. Frontiersin Cell and Developmental Biology, 2021, 9, 661317. DOI: 10.3389/fcell.2021.661317

[67]Li N, Wang W, Zhou H, Wu Q, Duan M, et al. Ferritinophagy-mediated ferroptosis is involved in sepsis-induced cardiac injury. Free Radical Biology and Medicine, 2020, 160, 303-318. DOI: 10.1016/j.freeradbiomed.2020.08.009

[68]Ni S, Yuan Y, Qian Z, Zhong Z, Lv T, et al. Hypoxia inhibits rankl-induced ferritinophagy and protects osteoclasts from ferroptosis. Free Radical Biology and Medicine, 2021, 169, 271-282. DOI: 10.1016/j.freeradbiomed.2021.04.027

[69]Tan Y, Huang Y, Mei R, Mao F, Yang D, et al. HUCMSC-derived exosomes delivered BECN1 induces ferroptosis of hepatic stellate cells via regulating the xCT/GPX4 axis. Cell Death & Disease, 2022, 13(4), 319. DOI: 10.1038/s41419-022-04764-2

[70]Yang RZ, Xu WN, Zheng HL, Zheng XF, Li B, et al. Exosomes derived from vascular endothelial cells antagonize glucocorticoid-induced osteoporosis by inhibiting ferritinophagy with resultant limited ferroptosis of osteoblasts. Journal of Cellular Physiology, 2021, 236(9), 6691-6705. DOI: 10.1002/jcp.30331

[71]Du X, Dong R, Wu Y, Ni B. Physiological effects of ferroptosis on organ fibrosis. Oxidative Medicine and Cellular Longevity, 2022, 2022(1), 5295434. DOI: 10.1155/2022/5295434

[72]Zhang H, Deng T, Liu R, Ning T, Yang H, et al. CAF secreted miR-522 suppresses ferroptosis and promotes acquired chemo-resistance in gastric cancer. Molecular Cancer, 2020, 19(1), 43. DOI: 10.1186/s12943-020-01168-8

[73]Xia J, Song X, Meng J, Lou D. Endothelial progenitor cells-derived exosomes transfer microRNA-30e-5p to regulate Erastin-induced ferroptosis in human umbilical vein endothelial cells via the specificity protein 1/adenosine monophosphate-activated protein kinase axis. Bioengineered, 2022, 13(2), 3566-3580. DOI: 10.1080/21655979.2022.2025519

[74]Zhang JK, Zhang Z, Guo ZA, Fu Y, Chen XJ, et al. The BMSC-derived exosomal lncRNA miR9-3hg suppresses cardiomyocyte ferroptosis in ischemia-reperfusion mice via the Pum2/PRDX6 axis. Nutrition, Metabolism and Cardiovascular Diseases, 2022, 32(2), 515-527. DOI: 10.1016/j.numecd.2021.10.017

[75]Lu B, Chen XB, Hong YC, Zhu H, He QJ, et al. Identification of PRDX6 as a regulator of ferroptosis. Acta Pharmacologica Sinica, 2019, 40(10), 1334-1342. DOI: 10.1038/s41401-019-0233-9

[76]Sadri F, Hosseini SF, Aghayei A, Fereidouni M, Rezaei Z. The tumor suppressor roles and mechanisms of miR-491 in human cancers. DNA and Cell Biology, 2022, 41(9), 810-823. DOI: 10.1089/dna.2022.0274

[77]Ranjbaran J, Safarpour H, Nomiri S, Tavakoli T, Rezaei Z, et al. Experimental validation of in silico analysis estimated the reverse effect of upregulated hsa-miR-106a-5p and hsa-miR-223-3p on SLC4A4 gene expression in Iranian patients with colorectal adenocarcinoma by RT-qPCR. Cancer Medicine, 2023, 12(6), 7005-7018. DOI: 10.1002/cam4.5499

[78]Zheng P, Chen L, Yuan X, Luo Q, Liu Y, et al. Exosomal transfer of tumor-associated macrophage-derived miR-21 confers cisplatin resistance in gastric cancer cells. Journal of Experimental & Clinical Cancer Research, 2017, 36, 1-13. DOI: 10.1186/s13046-017-0528-y

[79]Du J, Liang Y, Li J, Zhao JM, Lin XY. Gastric cancer cell-derived exosomal microRNA-23a promotes angiogenesis by targeting PTEN. Frontiers in Oncology, 2020, 10, 326. DOI: 10.3389/fonc.2020.00326

[80]Wang W, Wang T, Zhang Y, Deng T, Zhang H, et al. Gastric cancer secreted miR-214-3p inhibits the anti-angiogenesis effect of apatinib by suppressing ferroptosis in vascular endothelial cells. Oncology Research, 2024, 32(3), 489-502. DOI: 10.32604/or.2023.046676

[81]Chen J, Zhang K, Zhi Y, Wu Y, Chen B, et al. Tumor-derived exosomal miR-19b-3p facilitates M2 macrophage polarization and exosomal LINC00273 secretion to promote lung adenocarcinoma metastasis via Hippo pathway. Clinical and Translational Medicine, 2021, 11(9), e478. DOI: 10.1002/ctm2.478

[82]Dai X, Hu Y, Sun C, Wang Y, Sun Z, et al. Qizhu Jianwei decoction triggers ferroptosis by exosome-mediated miR-199-3p/ACSL4 signaling pathways. Journal of Ethnopharmacology, 2025, 344, 119529. DOI: 10.1016/j.jep.2025.119529

[83]Zhang H, Wang M, He Y, Deng T, Liu R, et al. Chemotoxicity-induced exosomal lncFERO regulates ferroptosis and stemness in gastric cancer stem cells. Cell Death & Disease, 2021, 12(12), 1116. DOI: 10.1038/s41419-021-04406-z

[84]Gu R, Xia Y, Li P, Zou D, Lu K, et al. Ferroptosis and its role in gastric cancer. Frontiersin Cell and Developmental Biology, 2022, 10, 860344. DOI: 10.3389/fcell.2022.860344

[85]Qu X, Liu B, Wang L, Liu L, Zhao W, et al. Loss of cancer-associated fibroblast-derived exosomal DACT3-AS1 promotes malignant transformation and ferroptosis-mediated oxaliplatin resistance in gastric cancer. Drug Resistance Updates, 2023, 68, 100936. DOI: 10.1016/j.drup.2023.100936

[86]Li Y, Zhu Y, Sheng P, Guo X, Li X, et al. Mechanism of gastric cancer cell-derived exosomal circPDSS1 promoting ferroptosis of natural killer cells by regulating miR-1278/GOT1 molecular axis. 2024, 1-26. DOI: 10.21203/rs.3.rs-3865289/v1

[87]Shang Z, Luo Z, Wang Y, Liu Q, Xin Y, et al. CircHIPK3 contributes to cisplatin resistance in gastric cancer by blocking autophagy-dependent ferroptosis. Journal of Cellular Physiology, 2023, 238(10), 2407-2424. DOI: 10.1002/jcp.31093

[88]Wu J, Li Z, Wu Y, Cui N. The crosstalk between exosomes and ferroptosis: A review. Cell Death Discovery, 2024, 10(1), 170. DOI: 10.1038/s41420-024-01938-z

[89]Ni H, Qin H, Sun C, Liu Y, Ruan G, et al. MiR-375 reduces the stemness of gastric cancer cells through triggering ferroptosis. Stem Cell Research & Therapy, 2021, 12(1), 325. DOI: 10.1186/s13287-021-02394-7

[90]Jin W, Liu J, Yang J, Feng Z, Feng Z, et al. Identification of a key ceRNA network associated with ferroptosis in gastric cancer. Scientific Reports, 2022, 12(1), 20088. DOI: 10.1038/s41598-022-24402-3

[91]Liu Y, Miao R, Xia J, Zhou Y, Yao J, et al. Infection of Helicobacter pylori contributes to the progression of gastric cancer through ferroptosis. Cell Death Discovery, 2024, 10(1), 1-10. DOI: 10.1038/s41420-024-02253-3

[92]Meng K, Song J, Qi F, Li J, Fang Z, et al. MT1G promotes iron autophagy and inhibits the function of gastric cancer cell lines by intervening in GPX4/SQSTM1. Scientific Reports, 2024, 14(1), 28539. DOI: 10.1038/s41598-024-80160-4

[93]Wu J, Luo D, Tou L, Xu H, Jiang C, et al. NEK2 affects the ferroptosis sensitivity of gastric cancer cells by regulating the expression of HMOX1 through Keap1/Nrf2. Molecular and Cellular Biochemistry, 2025, 480(1), 425-437. DOI: 10.1007/s11010-024-04960-y

[94]Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science, 2020, 367(6478), eaau6977. DOI: 10.1126/science.aau6977

[95]Song Y, Wu L, Yang C. Exosomal PD-L1: An effective liquid biopsy target to predict immunotherapy response. National Science Review, 2019, 6(6), 1103-1104. DOI: 10.1093/nsr/nwy154

[96]Yáñez-Mó M, Siljander PR-M, Andreu Z, Bedina Zavec A, Borràs FE, et al. Biological properties of extracellular vesicles and their physiological functions. Journal of Extracellular Vesicles, 2015, 4(1), 27066. DOI: 10.3402/jev.v4.27066

[97]Palakurthi SS, Shah B, Kapre S, Charbe N, Immanuel S, et al. A comprehensive review of challenges and advances in exosome-based drug delivery systems. Nanoscale Advances, 2024, 6(23), 5803-5826. DOI: 10.1039/d4na00501e

[98]Li J, Wang J, Chen Z. Emerging role of exosomes in cancer therapy: Progress and challenges. Molecular Cancer, 2025, 24(1), 13. DOI: 10.1186/s12943-024-02215-4

[99]Yu M, Gai C, Li Z, Ding D, Zheng J, et al. Targeted exosome‐encapsulated erastin induced ferroptosis in triple negative breast cancer cells. Cancer Science, 2019, 110(10), 3173-3182. DOI: 10.1111/cas.14181

[100]Song Z, Jia G, Ma P, Cang S. Exosomal miR-4443 promotes cisplatin resistance in non-small cell lung carcinoma by regulating FSP1 m6A modification-mediated ferroptosiss. Life Sciences, 2021, 276, 119399. DOI: 10.1016/j.lfs.2021.119399

[101]Strzyz P. Iron expulsion by exosomes drives ferroptosis resistance. Nature Reviews Molecular Cell Biology, 2020, 21(1), 4-5. DOI: 10.1038/s41580-019-0195-2

[102]Brown CW, Amante JJ, Chhoy P, Elaimy AL, Liu H, et al. Prominin2 drives ferroptosis resistance by stimulating iron export. Developmental Cell, 2019, 51(5), 575-586.e574. DOI: 10.1016/j.devcel.2019.10.007

[103]Patil SM, Sawant SS, Kunda NK. Exosomes as drug delivery systems: A brief overview and progress update. European Journal of Pharmaceutics and Biopharmaceutics, 2020, 154, 259-269. DOI: 10.1016/j.ejpb.2020.07.026

[104]Song Q, Peng S, Sun Z, Heng X, Zhu X. Temozolomide drives ferroptosis via a DMT1-dependent pathway in glioblastoma cells. Yonsei Medical Journal, 2021, 62(9), 843-849. DOI: 10.3349/ymj.2021.62.9.843

[105]Sanchez JI, Jiao J, Kwan SY, Veillon L, Warmoes MO, et al. Lipidomic profiles of plasma exosomes identify candidate biomarkers for early detection of hepatocellular carcinoma in patients with cirrhosis. Cancer Prevention Research, 2021, 14(10), 955-962. DOI: 10.1158/1940-6207.CAPR-20-0612

[106]Yi X, Li Y, Hu X, Wang F, Liu T. Changes in phospholipid metabolism in exosomes of hormone-sensitive and hormone-resistant prostate cancer cells. Journal of Cancer, 2021, 12(10), 2893. DOI: 10.7150/jca.48906

[107]Zhu Q, Li H, Ao Z, Xu H, Luo J, et al. Lipidomic identification of urinary extracellular vesicles for non-alcoholic steatohepatitis diagnosis. Journal of Nanobiotechnology, 2022, 20(1), 349. DOI: 10.1186/s12951-022-01540-4

[108]Dai E, Han L, Liu J, Xie Y, Kroemer G, et al. Autophagy-dependent ferroptosis drives tumor-associated macrophage polarization via release and uptake of oncogenic KRAS protein. Autophagy, 2020, 16(11), 2069-2083. DOI: 10.1080/15548627.2020.1714209

Downloads

Published

2025-05-09

Issue

Section

Articles