{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T18:30:49Z","timestamp":1775586649392,"version":"3.50.1"},"reference-count":43,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T00:00:00Z","timestamp":1669766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University Hospital Erlangen","award":["P110"],"award-info":[{"award-number":["P110"]}]},{"name":"University Hospital Erlangen","award":["BO1573"],"award-info":[{"award-number":["BO1573"]}]},{"DOI":"10.13039\/501100001659","name":"German Research Association (DFG)","doi-asserted-by":"publisher","award":["P110"],"award-info":[{"award-number":["P110"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Association (DFG)","doi-asserted-by":"publisher","award":["BO1573"],"award-info":[{"award-number":["BO1573"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cutaneous malignant melanoma is a highly proliferative and aggressive skin cancer with a steadily increasing incidence and a low long-term survival rate after metastatic progression. The protein MAGOH and its highly identical homologue MAGOHB are core components of the exon junction complex (EJC), which regulates splicing, stability and translation of mRNAs. The EJC, and especially MAGOH, has been shown to be involved in the development and progression of several cancers. In melanoma, the expression and function of both homologues remain essentially unexplored. This study identifies high MAGOH and MAGOHB protein expression in cutaneous melanoma cell lines and patient derived tissue samples. An siRNA-mediated knockdown of MAGOH significantly inhibits melanoma cell proliferation. The loss of MAGOH does not affect cell cycle progression, but induces apoptosis, an effect that is enhanced by a simultaneous knockdown of MAGOH and MAGOHB. MAGOH and MAGOHB do not influence the expression of the pro-apoptotic protein Bcl-XS or exon skipping. However, the knockdown of MAGOH and MAGOHB strongly decreases nonsense-mediated decay (NMD) activity, leading to an upregulation of the pro-apoptotic protein GADD45A. In conclusion, simultaneous inhibition of MAGOH and MAGOHB expression substantially affects cell survival, indicating both MAGOH homologues as promising new targets for the treatment of melanoma.<\/jats:p>","DOI":"10.3390\/cells11233859","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T08:46:41Z","timestamp":1669798001000},"page":"3859","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["MAGOH and MAGOHB Knockdown in Melanoma Cells Decreases Nonsense-Mediated Decay Activity and Promotes Apoptosis via Upregulation of GADD45A"],"prefix":"10.3390","volume":"11","author":[{"given":"Agnes","family":"Soederberg","sequence":"first","affiliation":[{"name":"Institute of Biochemistry, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), Fahrstra\u00dfe 17, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tina","family":"Mei\u00dfgeier","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), Fahrstra\u00dfe 17, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8147-394X","authenticated-orcid":false,"given":"Anja Katrin","family":"Bosserhoff","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), Fahrstra\u00dfe 17, 91054 Erlangen, Germany"},{"name":"Comprehensive Cancer Center (CCC) Erlangen-EMN, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8581-684X","authenticated-orcid":false,"given":"Lisa","family":"Linck-Paulus","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), Fahrstra\u00dfe 17, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA. Cancer J. Clin."},{"key":"ref_2","first-page":"1","article-title":"Melanoma-clinical, dermatoscopical, and histopathological morphological characteristics","volume":"22","author":"Buljan","year":"2014","journal-title":"Acta Dermatovenerol. Croat."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nrc.2016.37","article-title":"From melanocytes to melanomas","volume":"16","author":"Shain","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1101\/gad.191999.112","article-title":"Melanoma: From mutations to medicine","volume":"26","author":"Tsao","year":"2012","journal-title":"Genes Dev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1111\/pcmr.12412","article-title":"Genetics of melanocytic nevi","volume":"28","author":"Roh","year":"2015","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1111\/j.1365-2133.2006.07564.x","article-title":"Transcriptional profiles in melanocytes from clinically unaffected skin distinguish the neoplastic growth pattern in patients with melanoma","volume":"156","author":"Magnoni","year":"2007","journal-title":"Br. J. Dermatol."},{"key":"ref_7","unstructured":"Matthews, N.H., Li, W.-Q., Qureshi, A.A., Weinstock, M.A., and Cho, E. (2017). Epidemiology of Melanoma. Cutaneous Melanoma: Etiology and Therapy, Codon Publications."},{"key":"ref_8","unstructured":"(2022, November 18). Europe. The Cancer Atlas. Available online: https:\/\/canceratlas.cancer.org\/the-burden\/europe\/."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/S0140-6736(18)31559-9","article-title":"Melanoma","volume":"392","author":"Schadendorf","year":"2018","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1111\/j.1468-3083.2011.04029.x","article-title":"Growth rate as an independent prognostic factor in localized invasive cutaneous melanoma","volume":"25","author":"Nagore","year":"2011","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1111\/pcmr.12890","article-title":"Speed rate (SR) as a new dynamic index of melanoma behavior","volume":"33","author":"Gualdi","year":"2020","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_12","unstructured":"Melanoma Survival Rates (2022, October 05). Melanoma Survival Statistics. Available online: https:\/\/www.cancer.org\/cancer\/melanoma-skin-cancer\/detection-diagnosis-staging\/survival-rates-for-melanoma-skin-cancer-by-stage.html."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2017\/2606271","article-title":"Skin Cancer and Its Treatment: Novel Treatment Approaches with Emphasis on Nanotechnology","volume":"2017","author":"Orthaber","year":"2017","journal-title":"J. Nanomater."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Schlautmann, L.P., and Gehring, N.H. (2020). A Day in the Life of the Exon Junction Complex. Biomolecules, 10.","DOI":"10.3390\/biom10060866"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.cell.2009.02.001","article-title":"Pre-mRNA Processing Reaches Back toTranscription and Ahead to Translation","volume":"136","author":"Moore","year":"2009","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/ng.3664","article-title":"The rules and impact of nonsense-mediated mRNA decay in human cancers","volume":"48","author":"Lindeboom","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_17","first-page":"27","article-title":"Regulation of alternative splicing and the case of Bcl-x","volume":"48","author":"Shkreta","year":"2015","journal-title":"Pak. J. Biochem. Mol. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.molcel.2018.09.033","article-title":"Exon Junction Complex Shapes the Transcriptome by Repressing Recursive Splicing","volume":"72","author":"Blazquez","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1186\/s13059-014-0551-7","article-title":"Transcriptome-wide modulation of splicing by the exon junction complex","volume":"15","author":"Wang","year":"2014","journal-title":"Genome Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.4161\/rna.25827","article-title":"Two mammalian MAGOH genes contribute to exon junction complex composition and nonsense-mediated decay","volume":"10","author":"Singh","year":"2013","journal-title":"RNA Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1177\/1535370213494646","article-title":"Depletion of RNA-binding protein RBM8A (Y14) causes cell cycle deficiency and apoptosis in human cells","volume":"238","author":"Ishigaki","year":"2013","journal-title":"Exp. Biol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1038\/s41588-018-0155-3","article-title":"Genome-scale analysis identifies paralog lethality as a vulnerability of chromosome 1p loss in cancer","volume":"50","author":"Viswanathan","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Otani, Y., Fujita, K.I., Kameyama, T., and Mayeda, A. (2021). The Exon Junction Complex Core Represses Cancer-Specific Mature mRNA Re-splicing: A Potential Key Role in Terminating Splicing. Int. J. Mol. Sci., 22.","DOI":"10.1101\/2021.04.01.438154"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"12723","DOI":"10.2147\/OTT.S263913","article-title":"MAGOH\/MAGOHB Inhibits the Tumorigenesis of Gastric Cancer via Inactivation of b-RAF\/MEK\/ERK Signaling","volume":"13","author":"Zhou","year":"2020","journal-title":"Onco. Targets Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.ydbio.2013.01.004","article-title":"The EJC component Magoh regulates proliferation and expansion of neural crest-derived melanocytes","volume":"375","author":"Silver","year":"2013","journal-title":"Dev. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4111","DOI":"10.1038\/s41598-018-22484-6","article-title":"Down-regulation of GADD45A enhances chemosensitivity in melanoma","volume":"8","author":"Liu","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_27","first-page":"1","article-title":"A previously unknown Argonaute 2 variant positively modulates the viability of melanoma cells","volume":"79","author":"Pieger","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"L\u00e4mmerhirt, L., Kappelmann-fenzl, M., Fischer, S., Pommer, M., Zimmermann, T., Kluge, V., Matthies, A., Kuphal, S., and Bosserhoff, A.K. (2022). Knockdown of Lamin B1 and the Corresponding Lamin B Receptor Leads to Changes in Heterochromatin State and Senescence Induction in Malignant Melanoma. Cells, 11.","DOI":"10.3390\/cells11142154"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1002\/cyto.990010114","article-title":"A model for the computer analysis of synchronous DNA distributions obtained by flow cytometry","volume":"1","author":"Fox","year":"1980","journal-title":"Cytometry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e148","DOI":"10.1093\/nar\/gkl967","article-title":"A bichromatic fluorescent reporter for cell-based screens of alternative splicing","volume":"34","author":"Orengo","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e33178","DOI":"10.7554\/eLife.33178","article-title":"ICE1 promotes the link between splicing and nonsense-mediated mRNA decay","volume":"7","author":"Baird","year":"2018","journal-title":"Elife"},{"key":"ref_32","unstructured":"Schagat, T., Paguio, A., and Kopish, K. (2022, October 13). Normalizing Genetic Reporter Assays: Approaches and Considerations for Increasing Consistency and Statistical Significance. Available online: https:\/\/www.promega.de\/-\/media\/files\/resources\/cell-notes\/cn017\/normalizing-genetic-reporter-assays.pdf?rev=56fc83d2f445401ea1d003cce3f51be7&sc_lang=en."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1002\/ijc.34254","article-title":"Nuclear AREG affects a low-proliferative phenotype and contributes to drug resistance of melanoma","volume":"151","author":"Seefried","year":"2022","journal-title":"Int. J. Cancer"},{"key":"ref_34","unstructured":"(2021, October 05). Expression of MAGOH in Melanoma\u2014The Human Protein Atlas. Available online: https:\/\/www.proteinatlas.org\/ENSG00000162385-MAGOH\/pathology\/melanoma."},{"key":"ref_35","unstructured":"(2021, October 05). Expression of MAGOHB in Melanoma\u2014The Human Protein Atlas. Available online: https:\/\/www.proteinatlas.org\/ENSG00000111196-MAGOHB\/pathology\/melanoma."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Tissue-based map of the human proteome","volume":"347","author":"Fagerberg","year":"2015","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1128\/MCB.06130-11","article-title":"Proteins Associated with the Exon Junction Complex Also Control the Alternative Splicing of Apoptotic Regulators","volume":"32","author":"Michelle","year":"2012","journal-title":"Mol. Cell. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7554\/eLife.12876","article-title":"Degradation of Gadd45 mRNA by nonsense-mediated decay is essential for viability","volume":"5","author":"Nelson","year":"2016","journal-title":"Elife"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/nature10762","article-title":"Clonal evolution in cancer","volume":"481","author":"Greaves","year":"2012","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Nogueira, G., Fernandes, R., Garc\u00eda-Moreno, J.F., and Rom\u00e3o, L. (2021). Nonsense-mediated RNA decay and its bipolar function in cancer. Mol. Cancer, 20.","DOI":"10.1186\/s12943-021-01364-0"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"388","DOI":"10.2174\/138920309788922216","article-title":"Diverse roles of GADD45alpha in stress signaling","volume":"10","author":"Gao","year":"2009","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4614-8289-5_1","article-title":"Gadd45 in Stress Signaling, Cell Cycle Control, and Apoptosis","volume":"Volume 793","author":"Salvador","year":"2013","journal-title":"Advances in Experimental Medicine and Biology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3800","DOI":"10.1038\/s41467-020-17526-5","article-title":"Escape from nonsense-mediated decay associates with anti-tumor immunogenicity","volume":"11","author":"Litchfield","year":"2020","journal-title":"Nat. Commun."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/23\/3859\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:30:32Z","timestamp":1760146232000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/23\/3859"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,30]]},"references-count":43,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["cells11233859"],"URL":"https:\/\/doi.org\/10.3390\/cells11233859","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,30]]}}}