Cargando…

MAGOH and MAGOHB Knockdown in Melanoma Cells Decreases Nonsense-Mediated Decay Activity and Promotes Apoptosis via Upregulation of GADD45A

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), w...

Descripción completa

Detalles Bibliográficos
Autores principales: Soederberg, Agnes, Meißgeier, Tina, Bosserhoff, Anja Katrin, Linck-Paulus, Lisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9738831/
https://www.ncbi.nlm.nih.gov/pubmed/36497117
http://dx.doi.org/10.3390/cells11233859
_version_ 1784847647805276160
author Soederberg, Agnes
Meißgeier, Tina
Bosserhoff, Anja Katrin
Linck-Paulus, Lisa
author_facet Soederberg, Agnes
Meißgeier, Tina
Bosserhoff, Anja Katrin
Linck-Paulus, Lisa
author_sort Soederberg, Agnes
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9738831
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-97388312022-12-11 MAGOH and MAGOHB Knockdown in Melanoma Cells Decreases Nonsense-Mediated Decay Activity and Promotes Apoptosis via Upregulation of GADD45A Soederberg, Agnes Meißgeier, Tina Bosserhoff, Anja Katrin Linck-Paulus, Lisa Cells Article 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. MDPI 2022-11-30 /pmc/articles/PMC9738831/ /pubmed/36497117 http://dx.doi.org/10.3390/cells11233859 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Soederberg, Agnes
Meißgeier, Tina
Bosserhoff, Anja Katrin
Linck-Paulus, Lisa
MAGOH and MAGOHB Knockdown in Melanoma Cells Decreases Nonsense-Mediated Decay Activity and Promotes Apoptosis via Upregulation of GADD45A
title MAGOH and MAGOHB Knockdown in Melanoma Cells Decreases Nonsense-Mediated Decay Activity and Promotes Apoptosis via Upregulation of GADD45A
title_full MAGOH and MAGOHB Knockdown in Melanoma Cells Decreases Nonsense-Mediated Decay Activity and Promotes Apoptosis via Upregulation of GADD45A
title_fullStr MAGOH and MAGOHB Knockdown in Melanoma Cells Decreases Nonsense-Mediated Decay Activity and Promotes Apoptosis via Upregulation of GADD45A
title_full_unstemmed MAGOH and MAGOHB Knockdown in Melanoma Cells Decreases Nonsense-Mediated Decay Activity and Promotes Apoptosis via Upregulation of GADD45A
title_short MAGOH and MAGOHB Knockdown in Melanoma Cells Decreases Nonsense-Mediated Decay Activity and Promotes Apoptosis via Upregulation of GADD45A
title_sort magoh and magohb knockdown in melanoma cells decreases nonsense-mediated decay activity and promotes apoptosis via upregulation of gadd45a
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9738831/
https://www.ncbi.nlm.nih.gov/pubmed/36497117
http://dx.doi.org/10.3390/cells11233859
work_keys_str_mv AT soederbergagnes magohandmagohbknockdowninmelanomacellsdecreasesnonsensemediateddecayactivityandpromotesapoptosisviaupregulationofgadd45a
AT meißgeiertina magohandmagohbknockdowninmelanomacellsdecreasesnonsensemediateddecayactivityandpromotesapoptosisviaupregulationofgadd45a
AT bosserhoffanjakatrin magohandmagohbknockdowninmelanomacellsdecreasesnonsensemediateddecayactivityandpromotesapoptosisviaupregulationofgadd45a
AT linckpauluslisa magohandmagohbknockdowninmelanomacellsdecreasesnonsensemediateddecayactivityandpromotesapoptosisviaupregulationofgadd45a