{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T19:59:23Z","timestamp":1776369563420,"version":"3.51.2"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T00:00:00Z","timestamp":1740700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Cutaneous melanoma is a type of malignant tumor that is challenging to predict and is readily stimulated by various factors. Oxidative stress can induce damage and alterations in melanocytes, subsequently triggering immune responses. Given that oxidative stress is a prevalent tumor stimulus, we aimed to enhance melanoma prediction by identifying lncRNA signatures associated with oxidative stress.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We screened for oxidative stress-related lncRNAs that could improve melanoma patient prognosis using the TCGA and GTEx databases. Utilizing differentially expressed oxidative stress-related lncRNAs (DE-OSlncRNAs), we constructed a Lasso regression model. The accuracy of the model was validated using univariate and multivariate regression, Kaplan-Meier (K-M) curves, and ROC curves. Subsequently, we conducted immune infiltration analysis, immune checkpoint differential analysis, IC50 pharmaceutical analysis, and gene set enrichment analysis. Investigating the effects of the target gene on melanoma using fluorescence in situ hybridization (FISH), quantitative real-time PCR (qRT-PCR), Edu assay, wound healing assay, transwell assay, flow cytometry, and reactive oxygen species (ROS) detection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirteen lncRNAs were identified as significant prognostic factors. Four oxidative stress-related lncRNAs (<jats:italic>COPDA1<\/jats:italic>, <jats:italic>LINC02132<\/jats:italic>, <jats:italic>LINC02812<\/jats:italic>, and <jats:italic>MIR205HG<\/jats:italic>) were further validated by fluorescence in situ hybridization (FISH), with results consistent with our data analysis. <jats:italic>LINC02132<\/jats:italic> and <jats:italic>COPDA1<\/jats:italic> can influence the proliferation, invasion, migration, and apoptosis of melanoma. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings suggest that upregulation of the <jats:italic>LINC02132<\/jats:italic> or <jats:italic>COPDA1<\/jats:italic> genes elevates intracellular reactive oxygen species (ROS) levels in melanoma cells, suppresses tumor cell proliferation, migration, and invasion, and promotes apoptosis. These results suggest a novel therapeutic strategy for melanoma treatment.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1558292","type":"journal-article","created":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T07:18:53Z","timestamp":1740727133000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Inhibiting melanoma tumor growth: the role of oxidative stress-associated LINC02132 and COPDA1 long non-coding RNAs"],"prefix":"10.3389","volume":"16","author":[{"given":"JingWen","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MingZhu","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ZhenZhen","family":"Mu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ZhengXiu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"RuiQun","family":"Qi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"XiuPing","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"HangHang","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.ccell.2019.12.007","article-title":"Epigenetic silencing of CDR1as drives IGF2BP3-mediated melanoma invasion and metastasis","volume":"37","author":"Hanniford","year":"2020","journal-title":"Cancer Cell"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.577072","article-title":"Immune microenvironment related competitive endogenous RNA network as powerful predictors for melanoma prognosis based on WGCNA analysis","volume":"10","author":"Cheng","year":"2020","journal-title":"Front Oncol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.11817\/j.issn.1672-7347.2021.200549","article-title":"Preliminary screening and correlation analysis for lncRNAs related to radiosensitivity in melanoma cells by inhibiting glycolysis","volume":"46","author":"Wang","year":"2021","journal-title":"Zhong nan da xue bao. Yi xue ban = J Cent South University. Med Sci"},{"key":"B4","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/s41388-021-02006-x","article-title":"The long non-coding RNA SAMMSON is essential for uveal melanoma cell survival","volume":"41","author":"Dewaele","year":"2022","journal-title":"Oncogene"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00944-19","article-title":"Vibrio cholerae virulence activator ToxR regulates manganese transport and resistance to reactive oxygen species","volume":"88","author":"Jiang","year":"2020","journal-title":"Infection Immun"},{"key":"B6","doi-asserted-by":"publisher","first-page":"102619","DOI":"10.1016\/j.redox.2023.102619","article-title":"ROS-lowering doses of vitamins C and A accelerate Malignant melanoma metastasis","volume":"60","author":"Kashif","year":"2023","journal-title":"Redox Biol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.3390\/molecules28031509","article-title":"Cytotoxic and Antioxidant Activity of Hypericum perforatum L. Extracts against Human Melanoma Cells from Different Stages of Cancer Progression, Cultured under Normoxia and Hypoxia","volume":"28","author":"Brankiewicz","year":"2023","journal-title":"Molecules"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2353","DOI":"10.3390\/ijms24032353","article-title":"The assessment of the phototoxic action of chlortetracycline and doxycycline as a potential treatment of melanotic melanoma-biochemical and molecular studies on COLO 829 and G-361 cell lines","volume":"24","author":"Rok","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B9","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s12860-023-00466-5","article-title":"The dual role of Nrf2 in melanoma: a systematic review","volume":"24","author":"Malakoutikhah","year":"2023","journal-title":"BMC Mol Cell Biol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"887","DOI":"10.3390\/ijms24010887","article-title":"Oxidative stress and immune response in melanoma: ion channels as targets of therapy","volume":"24","author":"Remigante","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.790047","article-title":"A novel ferroptosis-related lncRNA prognostic model and immune infiltration features in skin cutaneous melanoma","volume":"9","author":"Sun","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202255069","article-title":"The mechanosensitive TRPV2 calcium channel promotes human melanoma invasiveness and metastatic potential","volume":"24","author":"Shoji","year":"2023","journal-title":"EMBO Rep"},{"key":"B13","doi-asserted-by":"publisher","first-page":"R646","DOI":"10.1152\/ajpregu.00247.2017","article-title":"The differential role of reactive oxygen species in early and late stages of cancer","volume":"313","author":"Assi","year":"2017","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5114\/wo.2021.112447","article-title":"Oxidative stress in melanogenesis and melanoma development","volume":"26","author":"Kami\u0144ski","year":"2022","journal-title":"Contemp Oncol (Pozn)"},{"key":"B15","doi-asserted-by":"publisher","first-page":"8994901","DOI":"10.1155\/2023\/8994901","article-title":"LINC01278 induces autophagy to inhibit tumour progression by suppressing the mTOR signalling pathway","volume":"2023","author":"Liu","year":"2023","journal-title":"Oxid Med Cell Longevity"},{"key":"B16","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.cell.2013.06.020","article-title":"lincRNAs: genomics, evolution, and mechanisms","volume":"154","author":"Ulitsky","year":"2013","journal-title":"Cell"},{"key":"B17","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1186\/s12943-022-01705-7","article-title":"lncRNA ZNRD1-AS1 promotes Malignant lung cell proliferation, migration, and angiogenesis via the miR-942\/TNS1 axis and is positively regulated by the m(6)A reader YTHDC2","volume":"21","author":"Wang","year":"2022","journal-title":"Mol Cancer"},{"key":"B18","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1186\/s12885-023-10828-z","article-title":"Identification of immunotherapy-related lncRNA signature for predicting prognosis, immunotherapy responses and drug candidates in bladder cancer","volume":"23","author":"Hui","year":"2023","journal-title":"BMC Cancer"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.18632\/aging.202450","article-title":"LncRNA MIR205HG regulates melanomagenesis via the miR-299-3p\/VEGFA axis","volume":"13","author":"Guo","year":"2021","journal-title":"Aging (Albany NY)"},{"key":"B20","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/s12935-020-01167-1","article-title":"Long non-coding RNA GAS5 accelerates oxidative stress in melanoma cells by rescuing EZH2-mediated CDKN1C downregulation","volume":"20","author":"Xu","year":"2020","journal-title":"Cancer Cell Int"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: a Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/kxj037","article-title":"Adjusting batch effects in microarray expression data using empirical Bayes methods","volume":"8","author":"Johnson","year":"2007","journal-title":"Biostatistics"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v033.i01","article-title":"Regularization paths for generalized linear models via coordinate descent","volume":"33","author":"Friedman","year":"2010","journal-title":"J Stat Softw"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa021967","article-title":"A gene-expression signature as a predictor of survival in breast cancer","volume":"347","author":"van de Vijver","year":"2002","journal-title":"N Engl J Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology. The Gene Ontology Consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat Genet"},{"key":"B28","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: kyoto encyclopedia of genes and genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7493-1_12","article-title":"Profiling tumor infiltrating immune cells with CIBERSORT","volume":"1711","author":"Chen","year":"2018","journal-title":"Methods Mol Biol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"e107468","DOI":"10.1371\/journal.pone.0107468","article-title":"pRRophetic: an R package for prediction of clinical chemotherapeutic response from tumor gene expression levels","volume":"9","author":"Geeleher","year":"2014","journal-title":"PloS One"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2012.287","article-title":"Sorafenib in advanced melanoma: a critical role for pharmacokinetics","volume":"107","author":"P\u00e9cuchet","year":"2012","journal-title":"Br J Cancer"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15010097","article-title":"Antimetastatic properties of prodigiosin and the BH3-mimetic obatoclax (GX15-070) in melanoma","volume":"15","author":"Espona-Fiedler","year":"2022","journal-title":"Pharmaceutics"},{"key":"B33","doi-asserted-by":"publisher","first-page":"101435","DOI":"10.1016\/j.xcrm.2024.101435","article-title":"Nilotinib in KIT-driven advanced melanoma: Results from the phase II single-arm NICAM trial","volume":"5","author":"Larkin","year":"2024","journal-title":"Cell Rep Med"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-019-02466-x","article-title":"Autologous monocyte-derived DC vaccination combined with cisplatin in stage III and IV melanoma patients: a prospective, randomized phase 2 trial","volume":"69","author":"Boudewijns","year":"2020","journal-title":"Cancer Immunol Immunother"},{"key":"B35","doi-asserted-by":"publisher","first-page":"5384","DOI":"10.3390\/ijms23105384","article-title":"Molecular pathology of skin melanoma: epidemiology, differential diagnostics, prognosis and therapy prediction","volume":"23","author":"T\u00edm\u00e1r","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-020-0490-7","article-title":"Through the looking glass and what you find there: making sense of comparative genomic hybridization and fluorescence in situ hybridization for melanoma diagnosis","volume":"33","author":"Miedema","year":"2020","journal-title":"Mod Pathol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"15003","DOI":"10.1038\/nrdp.2015.3","article-title":"Melanoma","volume":"1","author":"SChadendorf","year":"2015","journal-title":"Nat Rev Dis Primers"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.suc.2019.09.012","article-title":"Surgical considerations and systemic therapy of melanoma","volume":"100","author":"Gamboa","year":"2020","journal-title":"Surg Clinics North America"},{"key":"B39","doi-asserted-by":"publisher","first-page":"102499","DOI":"10.1016\/j.ctrv.2022.102499","article-title":"Mechanisms of resistance to immune checkpoint inhibitors in melanoma: What we have to overcome","volume":"113","author":"Ziogas","year":"2023","journal-title":"Cancer Treat Rev"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2014.03.034","article-title":"ROS function in redox signaling and oxidative stress","volume":"24","author":"Schieber","year":"2014","journal-title":"Curr Biol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2020.4616","article-title":"UV exposure and the risk of cutaneous melanoma in skin of color: A systematic review","volume":"157","author":"Lopes","year":"2021","journal-title":"JAMA Dermatol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/S0300-483X(03)00150-1","article-title":"UV-induced skin damage","volume":"189","author":"Ichihashi","year":"2003","journal-title":"Toxicology"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2012.160","article-title":"The long non-coding RNAs, a new cancer diagnostic and therapeutic gold mine","volume":"26","author":"Qi","year":"2013","journal-title":"Mod Pathol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.622294","article-title":"LncRNA-encoded peptide: functions and predicting methods","volume":"10","author":"Xing","year":"2020","journal-title":"Front Oncol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2021.02.002","article-title":"Long noncoding RNAs in human stemness and differentiation","volume":"31","author":"Mirzadeh Azad","year":"2021","journal-title":"Trends Cell Biol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1714","DOI":"10.3390\/ijms21051714","article-title":"Circulating RNAs as potential biomarkers in amyotrophic lateral sclerosis","volume":"21","author":"Ravnik-Glava\u010d","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/nature15726","article-title":"Oxidative stress inhibits distant metastasis by human melanoma cells","volume":"527","author":"Piskounova","year":"2015","journal-title":"Nature"},{"key":"B48","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1016\/j.ccell.2020.05.004","article-title":"Multi-phenotype CRISPR-cas9 screen identifies p38 kinase as a target for adoptive immunotherapies","volume":"37","author":"Gurusamy","year":"2020","journal-title":"Cancer Cell"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-023-01831-7","article-title":"Development and validation of ferroptosis-related lncRNA signature and immune-related gene signature for predicting the prognosis of cutaneous melanoma patients","volume":"28","author":"Xiong","year":"2023","journal-title":"Apoptosis"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2018-0269OC","article-title":"Long noncoding RNA COPDA1 promotes airway smooth muscle cell proliferation in chronic obstructive pulmonary disease","volume":"61","author":"Zheng","year":"2019","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B51","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1002\/1878-0261.13142","article-title":"LncRNA miR205HG hinders HNRNPA0 translation: anti-oncogenic effects in esophageal carcinoma","volume":"16","author":"Dong","year":"2021","journal-title":"Mol Oncol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.tranon.2019.10.018","article-title":"Checkpoint genes at the cancer side of the immunological synapse in bladder cancer","volume":"13","author":"Dobosz","year":"2020","journal-title":"Transl Oncol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-03054-1","article-title":"Anti-tumour immunity induces aberrant peptide presentation in melanoma","volume":"590","author":"Bartok","year":"2021","journal-title":"Nature"},{"key":"B54","doi-asserted-by":"publisher","first-page":"5386","DOI":"10.3390\/ijms24065386","article-title":"MicroRNA as a diagnostic tool, therapeutic target and potential biomarker in cutaneous Malignant melanoma detection-narrative review","volume":"24","author":"Poniewierska-Baran","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B55","doi-asserted-by":"publisher","first-page":"jkab157","DOI":"10.1093\/g3journal\/jkab157","article-title":"Membrane protein regulators of melanoma pulmonary colonization identified using a CRISPRa screen and spontaneous metastasis assay in mice","volume":"11","author":"Weyden","year":"2021","journal-title":"G3 Genes|Genomes|Genetics"},{"key":"B56","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/1476-4598-13-83","article-title":"Effects of AKT inhibitor therapy in response and resistance to BRAF inhibition in melanoma","volume":"13","author":"Lassen","year":"2014","journal-title":"Mol Cancer"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2022.11.044","article-title":"Risk of melanoma and nonmelanoma skin cancer with immunosuppressants, part I: Calcineurin inhibitors, thiopurines, IMDH inhibitors, mTOR inhibitors, and corticosteroids","volume":"88","author":"Kreher","year":"2023","journal-title":"J Am Acad Dermatol"},{"key":"B58","article-title":"Costunolide suppresses melanoma growth via the AKT\/mTOR pathway","volume":"11","author":"Huang","year":"2021","journal-title":"Am J Cancer Res"},{"key":"B59","doi-asserted-by":"publisher","first-page":"5863","DOI":"10.3390\/cancers13225863","article-title":"IGF1R\/IR mediates resistance to BRAF and MEK inhibitors in BRAF-mutant melanoma","volume":"13","author":"Patel","year":"2021","journal-title":"Cancers"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2021.02.005","article-title":"Effect of stress-induced polyploidy on melanoma reprogramming and therapy resistance","volume":"81","author":"Meierjohann","year":"2022","journal-title":"Semin Cancer Biol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1558292\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T07:18:59Z","timestamp":1740727139000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1558292\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,28]]},"references-count":60,"alternative-id":["10.3389\/fimmu.2025.1558292"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1558292","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,28]]},"article-number":"1558292"}}