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Proteome Analysis of USP7 Substrates Revealed Its Role in Melanoma Through PI3K/Akt/FOXO and AMPK Pathways

The ubiquitin-specific protease 7 (USP7), as a deubiquitinating enzyme, plays an important role in tumor progression by various mechanisms and serves as a potential therapeutic target. However, the functional role of USP7 in melanoma remains elusive. Here, we found that USP7 is overexpressed in huma...

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Autores principales: Gao, Lanyang, Zhu, Danli, Wang, Qin, Bao, Zheng, Yin, Shigang, Qiang, Huiyan, Wieland, Heinrich, Zhang, Jinyue, Teichmann, Alexander, Jia, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044529/
https://www.ncbi.nlm.nih.gov/pubmed/33869052
http://dx.doi.org/10.3389/fonc.2021.650165
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author Gao, Lanyang
Zhu, Danli
Wang, Qin
Bao, Zheng
Yin, Shigang
Qiang, Huiyan
Wieland, Heinrich
Zhang, Jinyue
Teichmann, Alexander
Jia, Jing
author_facet Gao, Lanyang
Zhu, Danli
Wang, Qin
Bao, Zheng
Yin, Shigang
Qiang, Huiyan
Wieland, Heinrich
Zhang, Jinyue
Teichmann, Alexander
Jia, Jing
author_sort Gao, Lanyang
collection PubMed
description The ubiquitin-specific protease 7 (USP7), as a deubiquitinating enzyme, plays an important role in tumor progression by various mechanisms and serves as a potential therapeutic target. However, the functional role of USP7 in melanoma remains elusive. Here, we found that USP7 is overexpressed in human melanoma by tissue microarray. We performed TMT-based quantitative proteomic analysis to evaluate the A375 human melanoma cells treated with siRNA of USP7. Our data revealed specific proteins as well as multiple pathways and processes that are impacted by USP7. We found that the phosphatidylinositol-3-kinases/Akt (PI3K-Akt), forkhead box O (FOXO), and AMP-activated protein kinase (AMPK) signaling pathways may be closely related to USP7 expression in melanoma. Moreover, knockdown of USP7 in A375 cells, particularly USP7 knockout using CRISPR-Cas9, verified that USP7 regulates cell proliferation in vivo and in vitro. The results showed that inhibition of USP7 increases expression of the AMPK beta (PRKAB1), caspase 7(CASP7), and protein phosphatase 2 subunit B R3 isoform (PPP2R3A), while attenuating expression of C subunit of vacuolar ATPase (ATP6V0C), and peroxisomal biogenesis factor 11 beta (PEX11B). In summary, these findings reveal an important role of USP7 in regulating melanoma progression via PI3K/Akt/FOXO and AMPK signaling pathways and implicate USP7 as an attractive anticancer target for melanoma.
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spelling pubmed-80445292021-04-15 Proteome Analysis of USP7 Substrates Revealed Its Role in Melanoma Through PI3K/Akt/FOXO and AMPK Pathways Gao, Lanyang Zhu, Danli Wang, Qin Bao, Zheng Yin, Shigang Qiang, Huiyan Wieland, Heinrich Zhang, Jinyue Teichmann, Alexander Jia, Jing Front Oncol Oncology The ubiquitin-specific protease 7 (USP7), as a deubiquitinating enzyme, plays an important role in tumor progression by various mechanisms and serves as a potential therapeutic target. However, the functional role of USP7 in melanoma remains elusive. Here, we found that USP7 is overexpressed in human melanoma by tissue microarray. We performed TMT-based quantitative proteomic analysis to evaluate the A375 human melanoma cells treated with siRNA of USP7. Our data revealed specific proteins as well as multiple pathways and processes that are impacted by USP7. We found that the phosphatidylinositol-3-kinases/Akt (PI3K-Akt), forkhead box O (FOXO), and AMP-activated protein kinase (AMPK) signaling pathways may be closely related to USP7 expression in melanoma. Moreover, knockdown of USP7 in A375 cells, particularly USP7 knockout using CRISPR-Cas9, verified that USP7 regulates cell proliferation in vivo and in vitro. The results showed that inhibition of USP7 increases expression of the AMPK beta (PRKAB1), caspase 7(CASP7), and protein phosphatase 2 subunit B R3 isoform (PPP2R3A), while attenuating expression of C subunit of vacuolar ATPase (ATP6V0C), and peroxisomal biogenesis factor 11 beta (PEX11B). In summary, these findings reveal an important role of USP7 in regulating melanoma progression via PI3K/Akt/FOXO and AMPK signaling pathways and implicate USP7 as an attractive anticancer target for melanoma. Frontiers Media S.A. 2021-03-31 /pmc/articles/PMC8044529/ /pubmed/33869052 http://dx.doi.org/10.3389/fonc.2021.650165 Text en Copyright © 2021 Gao, Zhu, Wang, Bao, Yin, Qiang, Wieland, Zhang, Teichmann and Jia https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Gao, Lanyang
Zhu, Danli
Wang, Qin
Bao, Zheng
Yin, Shigang
Qiang, Huiyan
Wieland, Heinrich
Zhang, Jinyue
Teichmann, Alexander
Jia, Jing
Proteome Analysis of USP7 Substrates Revealed Its Role in Melanoma Through PI3K/Akt/FOXO and AMPK Pathways
title Proteome Analysis of USP7 Substrates Revealed Its Role in Melanoma Through PI3K/Akt/FOXO and AMPK Pathways
title_full Proteome Analysis of USP7 Substrates Revealed Its Role in Melanoma Through PI3K/Akt/FOXO and AMPK Pathways
title_fullStr Proteome Analysis of USP7 Substrates Revealed Its Role in Melanoma Through PI3K/Akt/FOXO and AMPK Pathways
title_full_unstemmed Proteome Analysis of USP7 Substrates Revealed Its Role in Melanoma Through PI3K/Akt/FOXO and AMPK Pathways
title_short Proteome Analysis of USP7 Substrates Revealed Its Role in Melanoma Through PI3K/Akt/FOXO and AMPK Pathways
title_sort proteome analysis of usp7 substrates revealed its role in melanoma through pi3k/akt/foxo and ampk pathways
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044529/
https://www.ncbi.nlm.nih.gov/pubmed/33869052
http://dx.doi.org/10.3389/fonc.2021.650165
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