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CSN6 promotes tumorigenesis of gastric cancer by ubiquitin-independent proteasomal degradation of p16(INK4a)

OBJECTIVE: CSN6 is a vital subunit of the constitutive photomorphogenesis 9 (COP9) signalosome (CSN), which is responsible for development disorders and promotes ubiquitin-26S proteasome-dependent degradation in vitro and vivo. Its role in the tumor development of gastric cancer remains unclear. In...

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Autores principales: Du, Wenqi, Liu, Zongxiang, Zhu, Wentao, Li, Tongtong, Zhu, Zhiman, Wei, Lulu, Song, Jun, Pei, Dongsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Chinese Anti-Cancer Association 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743625/
https://www.ncbi.nlm.nih.gov/pubmed/31565481
http://dx.doi.org/10.20892/j.issn.2095-3941.2018.0410
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author Du, Wenqi
Liu, Zongxiang
Zhu, Wentao
Li, Tongtong
Zhu, Zhiman
Wei, Lulu
Song, Jun
Pei, Dongsheng
author_facet Du, Wenqi
Liu, Zongxiang
Zhu, Wentao
Li, Tongtong
Zhu, Zhiman
Wei, Lulu
Song, Jun
Pei, Dongsheng
author_sort Du, Wenqi
collection PubMed
description OBJECTIVE: CSN6 is a vital subunit of the constitutive photomorphogenesis 9 (COP9) signalosome (CSN), which is responsible for development disorders and promotes ubiquitin-26S proteasome-dependent degradation in vitro and vivo. Its role in the tumor development of gastric cancer remains unclear. In this study, we investigated the role of CSN6 in gastric cancer progression. METHODS: Human gastric cancer samples were collected and immunohistochemistry was performed to identify the role of CSN6 in gastric cancer. The cell proliferation was measured by CCK-8 and the EdU incorporation method. Immunofluorescence localization and a co-immunoprecipitation study were used to show the interaction between the protein CSN6 and p16. Ubiquitination assay was performed to validate whether ubiquitination is involved in CSN6-mediated p16 degradation. BALB/c nude mice were used to produce a tumor model in order to test the effect of CSN6 on cancer growth in vivo. RESULTS: CSN6 expression was dramatically increased in gastric cancer tissues compared with paired adjacent non-tumor tissues and CSN6 was correlated with worse overall and disease-specific survival. Additionally, we also found that CSN6 downregulated p16 protein expression, thereby promoting gastric cancer cell growth and proliferation. Moreover, CSN6 interacted with p16 and a proteasome activator REGγ (PA28γ), thereby facilitating ubiquitin-independent degradation of p16. CONCLUSIONS: CSN6 promoted the loss of p16-mediated tumor progression and played an important role in regulating ubiquitin-independent proteasomal degradation of p16.
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spelling pubmed-67436252019-09-27 CSN6 promotes tumorigenesis of gastric cancer by ubiquitin-independent proteasomal degradation of p16(INK4a) Du, Wenqi Liu, Zongxiang Zhu, Wentao Li, Tongtong Zhu, Zhiman Wei, Lulu Song, Jun Pei, Dongsheng Cancer Biol Med Original Article OBJECTIVE: CSN6 is a vital subunit of the constitutive photomorphogenesis 9 (COP9) signalosome (CSN), which is responsible for development disorders and promotes ubiquitin-26S proteasome-dependent degradation in vitro and vivo. Its role in the tumor development of gastric cancer remains unclear. In this study, we investigated the role of CSN6 in gastric cancer progression. METHODS: Human gastric cancer samples were collected and immunohistochemistry was performed to identify the role of CSN6 in gastric cancer. The cell proliferation was measured by CCK-8 and the EdU incorporation method. Immunofluorescence localization and a co-immunoprecipitation study were used to show the interaction between the protein CSN6 and p16. Ubiquitination assay was performed to validate whether ubiquitination is involved in CSN6-mediated p16 degradation. BALB/c nude mice were used to produce a tumor model in order to test the effect of CSN6 on cancer growth in vivo. RESULTS: CSN6 expression was dramatically increased in gastric cancer tissues compared with paired adjacent non-tumor tissues and CSN6 was correlated with worse overall and disease-specific survival. Additionally, we also found that CSN6 downregulated p16 protein expression, thereby promoting gastric cancer cell growth and proliferation. Moreover, CSN6 interacted with p16 and a proteasome activator REGγ (PA28γ), thereby facilitating ubiquitin-independent degradation of p16. CONCLUSIONS: CSN6 promoted the loss of p16-mediated tumor progression and played an important role in regulating ubiquitin-independent proteasomal degradation of p16. Chinese Anti-Cancer Association 2019-08 /pmc/articles/PMC6743625/ /pubmed/31565481 http://dx.doi.org/10.20892/j.issn.2095-3941.2018.0410 Text en Copyright 2019 Cancer Biology & Medicine http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Original Article
Du, Wenqi
Liu, Zongxiang
Zhu, Wentao
Li, Tongtong
Zhu, Zhiman
Wei, Lulu
Song, Jun
Pei, Dongsheng
CSN6 promotes tumorigenesis of gastric cancer by ubiquitin-independent proteasomal degradation of p16(INK4a)
title CSN6 promotes tumorigenesis of gastric cancer by ubiquitin-independent proteasomal degradation of p16(INK4a)
title_full CSN6 promotes tumorigenesis of gastric cancer by ubiquitin-independent proteasomal degradation of p16(INK4a)
title_fullStr CSN6 promotes tumorigenesis of gastric cancer by ubiquitin-independent proteasomal degradation of p16(INK4a)
title_full_unstemmed CSN6 promotes tumorigenesis of gastric cancer by ubiquitin-independent proteasomal degradation of p16(INK4a)
title_short CSN6 promotes tumorigenesis of gastric cancer by ubiquitin-independent proteasomal degradation of p16(INK4a)
title_sort csn6 promotes tumorigenesis of gastric cancer by ubiquitin-independent proteasomal degradation of p16(ink4a)
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743625/
https://www.ncbi.nlm.nih.gov/pubmed/31565481
http://dx.doi.org/10.20892/j.issn.2095-3941.2018.0410
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