{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:12:44Z","timestamp":1792091564110,"version":"4.4.0"},"reference-count":85,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T00:00:00Z","timestamp":1698364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020 research and innovation program","award":["860303"],"award-info":[{"award-number":["860303"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation program","award":["RTI2018-094969-B-I00"],"award-info":[{"award-number":["RTI2018-094969-B-I00"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation program","award":["101079264"],"award-info":[{"award-number":["101079264"]}]},{"name":"Spanish Ministry of Economy and Competitiveness MINECO","award":["860303"],"award-info":[{"award-number":["860303"]}]},{"name":"Spanish Ministry of Economy and Competitiveness MINECO","award":["RTI2018-094969-B-I00"],"award-info":[{"award-number":["RTI2018-094969-B-I00"]}]},{"name":"Spanish Ministry of Economy and Competitiveness MINECO","award":["101079264"],"award-info":[{"award-number":["101079264"]}]},{"name":"HORIZON-WIDERA-2021-ACCESS-03-01 EU Twining EVCA project","award":["860303"],"award-info":[{"award-number":["860303"]}]},{"name":"HORIZON-WIDERA-2021-ACCESS-03-01 EU Twining EVCA project","award":["RTI2018-094969-B-I00"],"award-info":[{"award-number":["RTI2018-094969-B-I00"]}]},{"name":"HORIZON-WIDERA-2021-ACCESS-03-01 EU Twining EVCA project","award":["101079264"],"award-info":[{"award-number":["101079264"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The human CERS2 gene encodes a ceramide synthase enzyme, known as CERS2 (ceramide synthase 2). This protein is also known as LASS2 (LAG1 longevity assurance homolog 2) and TMSG1 (tumor metastasis-suppressor gene 1). Although previously described as a tumor suppressor for different types of cancer, such as prostate or liver cancer, it has also been observed to promote tumor growth in adenocarcinoma. In this review, we focus on the influence of CERS2 in bladder cancer (BC), approaching the existing literature about its structure and activity, as well as the miRNAs regulating its expression. From a mechanistic point of view, different explanations for the role of CERS2 as an antitumor protein have been proposed, including the production of long-chain ceramides, interaction with vacuolar ATPase, and its function as inhibitor of mitochondrial fission. In addition, we reviewed the literature specifically studying the expression of this gene in both BC and biopsy-derived tumor cell lines, complementing this with an analysis of public gene expression data and its association with disease progression. We also discuss the importance of CERS2 as a biomarker and the presence of CERS2 mRNA in extracellular vesicles isolated from urine.<\/jats:p>","DOI":"10.3390\/ijms242115668","type":"journal-article","created":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T09:42:52Z","timestamp":1698399772000},"page":"15668","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Role of Longevity Assurance Homolog 2\/Ceramide Synthase 2 in Bladder Cancer"],"prefix":"10.3390","volume":"24","author":[{"given":"Clara","family":"Garcia-Vallicrosa","sequence":"first","affiliation":[{"name":"Exosomes Laboratory and Metabolomics Platform, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), 48160 Derio, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3133-0670","authenticated-orcid":false,"given":"Juan M.","family":"Falcon-Perez","sequence":"additional","affiliation":[{"name":"Exosomes Laboratory and Metabolomics Platform, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), 48160 Derio, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas Y Digestivas (CIBERehd), 28029 Madrid, Spain"},{"name":"IKERBASQUE, Basque Foundation for Science, 48013 Bilbao, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9769-4165","authenticated-orcid":false,"given":"Felix","family":"Royo","sequence":"additional","affiliation":[{"name":"Exosomes Laboratory and Metabolomics Platform, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), 48160 Derio, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas Y Digestivas (CIBERehd), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"277","DOI":"10.3322\/caac.20073","article-title":"Cancer statistics, 2010","volume":"60","author":"Jemal","year":"2010","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3875147","DOI":"10.1155\/2019\/3875147","article-title":"Evaluation of CERS2 Gene as a Potential Biomarker for Bladder Cancer","volume":"2019","author":"Aldoghachi","year":"2019","journal-title":"Dis. Markers"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1097\/CCO.0b013e3283446a11","article-title":"Bladder cancer","volume":"23","author":"Morgan","year":"2011","journal-title":"Curr. Opin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"179","DOI":"10.3390\/cancers6010179","article-title":"A Pilot Study on the Potential of RNA-Associated to Urinary Vesicles as a Suitable Non-Invasive Source for Diagnostic Purposes in Bladder Cancer","volume":"6","author":"Perez","year":"2014","journal-title":"Cancers"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7867","DOI":"10.1007\/s11033-023-08689-7","article-title":"Molecular classification of urothelial bladder carcinoma","volume":"50","author":"Schwarzova","year":"2023","journal-title":"Mol. Biol. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9743","DOI":"10.1038\/s41598-020-66747-7","article-title":"Assessment of Luminal and Basal Phenotypes in Bladder Cancer","volume":"10","author":"Guo","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1002\/jcb.24716","article-title":"Silencing of LASS2\/TMSG1 enhances invasion and metastasis capacity of prostate cancer cell","volume":"115","author":"Xu","year":"2014","journal-title":"J. Cell Biochem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"661","DOI":"10.3892\/ol.2016.5514","article-title":"LASS2 inhibits growth and invasion of bladder cancer by regulating ATPase activity","volume":"13","author":"Wang","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1007\/s12010-022-04234-7","article-title":"Identify Potential Urine Biomarkers for Bladder Cancer Prognosis Using NGS Data Analysis and Experimental Validation","volume":"195","author":"Ren","year":"2023","journal-title":"Appl. Biochem. Biotechnol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"13001","DOI":"10.1002\/jcp.27970","article-title":"High expression of LASS2 is associated with unfavorable prognosis in patients with ovarian cancer","volume":"234","author":"Sheng","year":"2019","journal-title":"J. Cell Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4423","DOI":"10.2147\/IJGM.S328376","article-title":"Bioinformatic Exploration for Prognostic Significance of Sphingolipid Metabolism-Related Genes in Invasive Ductal Carcinoma Using the Cancer Genome Atlas Cohort","volume":"14","author":"Kim","year":"2021","journal-title":"Int. J. Gen. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7204415","DOI":"10.1155\/2022\/7204415","article-title":"Prognostic Signature and Therapeutic Value Based on Membrane Lipid Biosynthesis-Related Genes in Breast Cancer","volume":"2022","author":"Xu","year":"2022","journal-title":"J. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"jcs228411","DOI":"10.1242\/jcs.228411","article-title":"Yeast ceramide synthases, Lag1 and Lac1, have distinct substrate specificity","volume":"132","author":"Megyeri","year":"2019","journal-title":"J. Cell Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"25001","DOI":"10.1074\/jbc.R600010200","article-title":"When do Lasses (longevity assurance genes) become CerS (ceramide synthases)?: Insights into the regulation of ceramide synthesis","volume":"281","author":"Futerman","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1360\/02yc9061","article-title":"Identification of tumor metastasisrelated gene TMSG-1 by mRNA differential display","volume":"45","author":"Ma","year":"2002","journal-title":"Sci. China C Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"D933","DOI":"10.1093\/nar\/gkac958","article-title":"Ensembl 2023","volume":"51","author":"Martin","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/s41419-021-03436-x","article-title":"Alternative splicing of ceramide synthase 2 alters levels of specific ceramides and modulates cancer cell proliferation and migration in Luminal B breast cancer subtype","volume":"12","author":"Pani","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5677","DOI":"10.1074\/jbc.M707386200","article-title":"Characterization of ceramide synthase 2: Tissue distribution, substrate specificity, and inhibition by sphingosine 1-phosphate","volume":"283","author":"Laviad","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.plipres.2016.03.006","article-title":"The enigma of ceramide synthase regulation in mammalian cells","volume":"63","author":"Wegner","year":"2016","journal-title":"Prog. Lipid Res."},{"key":"ref_21","first-page":"D845","article-title":"The DisGeNET knowledge platform for disease genomics: 2019 update","volume":"48","author":"Pinero","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Shiffman, D., Pare, G., Oberbauer, R., Louie, J.Z., Rowland, C.M., Devlin, J.J., Mann, J.F., and McQueen, M.J. (2014). A gene variant in CERS2 is associated with rate of increase in albuminuria in patients with diabetes from ONTARGET and TRANSCEND. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0106631"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1038\/s41467-019-09861-z","article-title":"Sex-specific and pleiotropic effects underlying kidney function identified from GWAS meta-analysis","volume":"10","author":"Graham","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1097\/CEJ.0000000000000551","article-title":"Association of rs8444 polymorphism in the LASS2 3\u2032-UTR and bladder cancer risk in Chinese population","volume":"29","author":"Huang","year":"2020","journal-title":"Eur. J. Cancer Prev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1002\/jcb.23359","article-title":"KLF6\/Sp1 initiates transcription of the tmsg-1 gene in human prostate carcinoma cells: An exon involved mechanism","volume":"113","author":"Gong","year":"2012","journal-title":"J. Cell Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.bcp.2014.10.007","article-title":"Ceramide synthases CerS4 and CerS5 are upregulated by 17beta-estradiol and GPER1 via AP-1 in human breast cancer cells","volume":"92","author":"Wegner","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/S0968-0004(02)02154-0","article-title":"TRAM, LAG1 and CLN8: Members of a novel family of lipid-sensing domains?","volume":"27","author":"Winter","year":"2002","journal-title":"Trends Biochem. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2511","DOI":"10.1016\/j.bbamcr.2013.04.010","article-title":"The complexity of sphingolipid biosynthesis in the endoplasmic reticulum","volume":"1833","author":"Tidhar","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"33931","DOI":"10.1074\/jbc.M608092200","article-title":"Necessary role for the Lag1p motif in (dihydro)ceramide synthase activity","volume":"281","author":"Spassieva","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"9912","DOI":"10.1074\/jbc.RA118.001936","article-title":"Eleven residues determine the acyl chain specificity of ceramide synthases","volume":"293","author":"Tidhar","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1016\/j.biocel.2013.06.004","article-title":"Ceramide metabolism in mouse tissue","volume":"45","author":"Schiffmann","year":"2013","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1006\/geno.2001.6614","article-title":"Cloning, mapping, and characterization of a human homologue of the yeast longevity assurance gene LAG1","volume":"77","author":"Pan","year":"2001","journal-title":"Genomics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1002\/jcb.24400","article-title":"A novel tumor metastasis suppressor gene LASS2\/TMSG1 interacts with vacuolar ATPase through its homeodomain","volume":"114","author":"Yu","year":"2013","journal-title":"J. Cell Biochem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1016\/j.cellsig.2010.04.006","article-title":"Ceramide synthases 2, 5, and 6 confer distinct roles in radiation-induced apoptosis in HeLa cells","volume":"22","author":"Mesicek","year":"2010","journal-title":"Cell Signal"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.biocel.2011.12.019","article-title":"Long chain ceramides and very long chain ceramides have opposite effects on human breast and colon cancer cell growth","volume":"44","author":"Hartmann","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"50","DOI":"10.18632\/oncoscience.531","article-title":"Alternative splicing of CERS2 promotes cell proliferation and migration in luminal B subtype breast cancer cells","volume":"8","author":"Pani","year":"2021","journal-title":"Oncoscience"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1093\/carcin\/bgp061","article-title":"Ceramide synthases and ceramide levels are increased in breast cancer tissue","volume":"30","author":"Schiffmann","year":"2009","journal-title":"Carcinogenesis"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"942","DOI":"10.3892\/etm.2013.892","article-title":"Expression of a tumor-associated gene, LASS2, in the human bladder carcinoma cell lines BIU-87, T24, EJ and EJ-M3","volume":"5","author":"Zhao","year":"2013","journal-title":"Exp. Ther. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1007\/s12032-011-0026-6","article-title":"Expression and prognostic significance of a new tumor metastasis suppressor gene LASS2 in human bladder carcinoma","volume":"29","author":"Wang","year":"2012","journal-title":"Med. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1002\/jcb.25086","article-title":"Overexpression of a Novel Tumor Metastasis Suppressor Gene TMSG1\/LASS2 Induces Apoptosis via a Caspase-dependent Mitochondrial Pathway","volume":"116","author":"Su","year":"2015","journal-title":"J. Cell Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41419-020-03281-4","article-title":"Targeting sphingosine kinase 1 (SK1) enhances oncogene-induced senescence through ceramide synthase 2 (CerS2)-mediated generation of very-long-chain ceramides","volume":"12","author":"Trayssac","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"30904","DOI":"10.1074\/jbc.M112.448852","article-title":"Protection of a ceramide synthase 2 null mouse from drug-induced liver injury: Role of gap junction dysfunction and connexin 32 mislocalization","volume":"288","author":"Park","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1002\/eji.201646623","article-title":"Ceramide synthase 2 facilitates S1P-dependent egress of thymocytes into the circulation in mice","volume":"47","author":"Rieck","year":"2017","journal-title":"Eur. J. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1242\/dev.094805","article-title":"Sphingosine 1-phosphate signalling","volume":"141","author":"Mendelson","year":"2014","journal-title":"Development"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/s41419-018-1298-y","article-title":"Sphingosine 1 phosphate receptor-1 (S1P1) promotes tumor-associated regulatory T cell expansion: Leading to poor survival in bladder cancer","volume":"10","author":"Liu","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4947","DOI":"10.1074\/jbc.M112.402719","article-title":"Ablation of ceramide synthase 2 causes chronic oxidative stress due to disruption of the mitochondrial respiratory chain","volume":"288","author":"Zigdon","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.7150\/jca.23087","article-title":"LASS2 regulates invasion and chemoresistance via ERK\/Drp1 modulated mitochondrial dynamics in bladder cancer cells","volume":"9","author":"Huang","year":"2018","journal-title":"J. Cancer"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.yexcr.2018.10.013","article-title":"MicroRNA-98 promotes drug resistance and regulates mitochondrial dynamics by targeting LASS2 in bladder cancer cells","volume":"373","author":"Luan","year":"2018","journal-title":"Exp. Cell Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2831","DOI":"10.1007\/s13277-014-2910-0","article-title":"LASS2\/TMSG1 inhibits growth and invasion of breast cancer cell in vitro through regulation of vacuolar ATPase activity","volume":"36","author":"Mei","year":"2015","journal-title":"Tumour. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-0716-2823-2_1","article-title":"miRNA Biogenesis and Regulation of Diseases: An Updated Overview","volume":"2595","author":"Vishnoi","year":"2023","journal-title":"Methods Mol. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Stavast, C.J., and Erkeland, S.J. (2019). The Non-Canonical Aspects of MicroRNAs: Many Roads to Gene Regulation. Cells, 8.","DOI":"10.3390\/cells8111465"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Ali Syeda, Z., Langden, S.S.S., Munkhzul, C., Lee, M., and Song, S.J. (2020). Regulatory Mechanism of MicroRNA Expression in Cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051723"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"9631","DOI":"10.1007\/s13277-015-3713-7","article-title":"miR-9 promotes cell proliferation and inhibits apoptosis by targeting LASS2 in bladder cancer","volume":"36","author":"Wang","year":"2015","journal-title":"Tumour. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.7754\/Clin.Lab.2020.201030","article-title":"MicroRNA-20a Targeting LASS2 Promotes the Proliferation, Invasiveness and Migration of Bladder Cancer","volume":"67","author":"Xiao","year":"2021","journal-title":"Clin. Lab."},{"key":"ref_55","first-page":"1813","article-title":"Repression of the miR-93-enhanced sensitivity of bladder carcinoma to chemotherapy involves the regulation of LASS2","volume":"9","author":"Liu","year":"2016","journal-title":"Onco Targets Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.gene.2019.02.083","article-title":"miR-3622a promotes proliferation and invasion of bladder cancer cells by downregulating LASS2","volume":"701","author":"Fu","year":"2019","journal-title":"Gene"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"515","DOI":"10.7754\/Clin.Lab.2017.171026","article-title":"Hsa-miR-3658 Promotes Cell Proliferation, Migration and Invasion by Effecting LASS2 in Bladder Cancer","volume":"64","author":"Luan","year":"2018","journal-title":"Clin. Lab."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"eabh2169","DOI":"10.1126\/sciadv.abh2169","article-title":"A single-cell type transcriptomics map of human tissues","volume":"7","author":"Karlsson","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"66","DOI":"10.14715\/cmb\/2018.64.11.12","article-title":"Expression profiles of proto-oncogene TWIST1 and tumor metastasis suppressor gene LASS2 in bladder cancer","volume":"64","author":"Yegin","year":"2018","journal-title":"Cell Mol. Biol. (Noisy-le-grand)"},{"key":"ref_60","first-page":"5149","article-title":"The role of LASS2 in regulating bladder cancer cell tumorigenicity in a nude mouse model","volume":"14","author":"Chen","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"de Bruijn, I., Kundra, R., Mastrogiacomo, B., Tran, T.N., Sikina, L., Mazor, T., Li, X., Ochoa, A., Zhao, G., and Lai, B. (2023). Analysis and Visualization of Longitudinal Genomic and Clinical Data from the AACR Project GENIE Biopharma Collaborative in cBioPortal. Cancer Res., Online ahead of print.","DOI":"10.1158\/0008-5472.CAN-23-0816"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"W556","DOI":"10.1093\/nar\/gkz430","article-title":"GEPIA2: An enhanced web server for large-scale expression profiling and interactive analysis","volume":"47","author":"Tang","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1476-4598-9-3","article-title":"Predictive value of progression-related gene classifier in primary non-muscle invasive bladder cancer","volume":"9","author":"Kim","year":"2010","journal-title":"Mol. Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3463","DOI":"10.1158\/0008-5472.CAN-09-4213","article-title":"Combined gene expression and genomic profiling define two intrinsic molecular subtypes of urothelial carcinoma and gene signatures for molecular grading and outcome","volume":"70","author":"Lindgren","year":"2010","journal-title":"Cancer Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3377","DOI":"10.1158\/1078-0432.CCR-12-0077-T","article-title":"A molecular taxonomy for urothelial carcinoma","volume":"18","author":"Sjodahl","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4040","DOI":"10.1158\/0008-5472.CAN-03-3620","article-title":"Gene expression in the urinary bladder: A common carcinoma in situ gene expression signature exists disregarding histopathological classification","volume":"64","author":"Dyrskjot","year":"2004","journal-title":"Cancer Res."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Lee, W.K., Maass, M., Quach, A., Poscic, N., Prangley, H., Pallott, E.C., Kim, J.L., Pierce, J.S., Ogretmen, B., and Futerman, A.H. (2022). Dependence of ABCB1 transporter expression and function on distinct sphingolipids generated by ceramide synthases-2 and -6 in chemoresistant renal cancer. J. Biol. Chem., 298.","DOI":"10.1016\/j.jbc.2021.101492"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Kong, T., He, Z., Wang, S., Jiang, C., Zhu, F., Gao, J., Li, L., Wang, Y., Xie, Q., and Li, Y. (2022). Diterpenoid DGA induces apoptosis via endoplasmic reticulum stress caused by changes in glycosphingolipid composition and inhibition of STAT3 in glioma cells. Biochem. Pharmacol., 205.","DOI":"10.1016\/j.bcp.2022.115254"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1083\/jcb.201211138","article-title":"Extracellular vesicles: Exosomes, microvesicles, and friends","volume":"200","author":"Raposo","year":"2013","journal-title":"J. Cell Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.tcb.2023.01.002","article-title":"Extracellular vesicles and nanoparticles: Emerging complexities","volume":"33","author":"Jeppesen","year":"2023","journal-title":"Trends Cell Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"101155","DOI":"10.1016\/j.mam.2022.101155","article-title":"Extracellular vesicles as personalized medicine","volume":"91","author":"Beetler","year":"2023","journal-title":"Mol. Asp. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"C29","DOI":"10.1152\/ajpcell.00280.2019","article-title":"Extracellular vesicles as biomarkers and therapeutic targets for cancer","volume":"318","author":"Urabe","year":"2020","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"13368","DOI":"10.1073\/pnas.0403453101","article-title":"Identification and proteomic profiling of exosomes in human urine","volume":"101","author":"Pisitkun","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e12093","DOI":"10.1002\/jev2.12093","article-title":"Urinary extracellular vesicles: A position paper by the Urine Task Force of the International Society for Extracellular Vesicles","volume":"10","author":"Erdbrugger","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1021\/pr700775x","article-title":"Isolation and identification of potential urinary microparticle biomarkers of bladder cancer","volume":"7","author":"Smalley","year":"2008","journal-title":"J. Proteome Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5960","DOI":"10.1038\/s41598-020-62753-x","article-title":"Urinary Exosomes from Bladder Cancer Patients Show a Residual Cancer Phenotype despite Complete Pathological Downstaging","volume":"10","author":"Hiltbrunner","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e10","DOI":"10.1038\/mtna.2011.2","article-title":"miR-1289 and \u201cZipcode\u201d-like Sequence Enrich mRNAs in Microvesicles","volume":"1","author":"Bolukbasi","year":"2012","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Casadome-Perales, A., Naya, S., Fernandez-Martinez, E., Mille, B.G., Guerrero-Valero, M., Peinado, H., Guix, F.X., Dotti, C.G., and Palomer, E. (2023). Neuronal Prosurvival Role of Ceramide Synthase 2 by Olidogendrocyte-to-Neuron Extracellular Vesicle Transfer. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065986"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1038\/s41467-022-29363-9","article-title":"Long-chain ceramides are cell non-autonomous signals linking lipotoxicity to endoplasmic reticulum stress in skeletal muscle","volume":"13","author":"McNally","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"7398","DOI":"10.3390\/curroncol30080536","article-title":"Do Cancer Genetics Impact Treatment Decision Making? Immunotherapy and Beyond in the Management of Advanced and Metastatic Urothelial Carcinoma","volume":"30","author":"Hui","year":"2023","journal-title":"Curr. Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41389-017-0013-7","article-title":"Unwrapping the genomic characteristics of urothelial bladder cancer and successes with immune checkpoint blockade therapy","volume":"7","author":"Cheng","year":"2018","journal-title":"Oncogenesis"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/j.cell.2018.07.036","article-title":"Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer","volume":"174","author":"Robertson","year":"2018","journal-title":"Cell"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Chiu, C.C., Chen, Y.C., Bow, Y.D., Chen, J.Y., Liu, W., Huang, J.L., Shu, E.D., Teng, Y.N., Wu, C.Y., and Chang, W.T. (2022). diTFPP, a Phenoxyphenol, Sensitizes Hepatocellular Carcinoma Cells to C(2)-Ceramide-Induced Autophagic Stress by Increasing Oxidative Stress and ER Stress Accompanied by LAMP2 Hypoglycosylation. Cancers, 14.","DOI":"10.3390\/cancers14102528"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"5682","DOI":"10.1073\/pnas.1316700111","article-title":"Bcl2L13 is a ceramide synthase inhibitor in glioblastoma","volume":"111","author":"Jensen","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.eururo.2019.09.006","article-title":"A Consensus Molecular Classification of Muscle-invasive Bladder Cancer","volume":"77","author":"Kamoun","year":"2020","journal-title":"Eur. Urol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/21\/15668\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:13:01Z","timestamp":1760130781000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/21\/15668"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,27]]},"references-count":85,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["ijms242115668"],"URL":"https:\/\/doi.org\/10.3390\/ijms242115668","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,27]]}}}