USP9X promotes apoptosis in cholangiocarcinoma by modulation expression of KIF1Bß via deubiquitinating EGLN3.
J Biomed Sci
; 28(1): 44, 2021 Jun 10.
Article
em En
| MEDLINE
| ID: mdl-34112167
ABSTRACT
BACKGROUND:
Cholangiocarcinoma represents the second most common primary liver malignancy. The incidence rate has constantly increased over the last decades. Cholangiocarcinoma silent nature limits early diagnosis and prevents efficient treatment.METHODS:
Immunoblotting and immunohistochemistry were used to assess the expression profiling of USP9X and EGLN3 in cholangiocarcinoma patients. ShRNA was used to silence gene expression. Cell apoptosis, cell cycle, CCK8, clone formation, shRNA interference and xenograft mouse model were used to explore biological function of USP9X and EGLN3. The underlying molecular mechanism of USP9X in cholangiocarcinoma was determined by immunoblotting, co-immunoprecipitation and quantitative real time PCR (qPCR).RESULTS:
Here we demonstrated that USP9X is downregulated in cholangiocarcinoma which contributes to tumorigenesis. The expression of USP9X in cholangiocarcinoma inhibited cell proliferation and colony formation in vitro as well as xenograft tumorigenicity in vivo. Clinical data demonstrated that expression levels of USP9X were positively correlated with favorable clinical outcomes. Mechanistic investigations further indicated that USP9X was involved in the deubiquitination of EGLN3, a member of 2-oxoglutarate and iron-dependent dioxygenases. USP9X elicited tumor suppressor role by preventing degradation of EGLN3. Importantly, knockdown of EGLN3 impaired USP9X-mediated suppression of proliferation. USP9X positively regulated the expression level of apoptosis pathway genes de through EGLN3 thus involved in apoptosis of cholangiocarcinoma.CONCLUSION:
These findings help to understand that USP9X alleviates the malignant potential of cholangiocarcinoma through upregulation of EGLN3. Consequently, we provide novel insight into that USP9X is a potential biomarker or serves as a therapeutic or diagnostic target for cholangiocarcinoma.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação Neoplásica da Expressão Gênica
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Cinesinas
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Apoptose
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Colangiocarcinoma
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Ubiquitina Tiolesterase
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Prolina Dioxigenases do Fator Induzível por Hipóxia
Tipo de estudo:
Prognostic_studies
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Screening_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
J Biomed Sci
Assunto da revista:
MEDICINA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China