c-Myb promotes growth and metastasis of colorectal cancer through c-fos-induced epithelial-mesenchymal transition.
Cancer Sci
; 110(10): 3183-3196, 2019 Oct.
Article
em En
| MEDLINE
| ID: mdl-31338937
ABSTRACT
c-Myb is a crucial transcription factor that participates in various biological functions; however, its role in colorectal cancer (CRC) remains poorly investigated. We first analyzed the expression and clinical significance of c-Myb in a retrospective cohort enrolling 132 CRC patients. Then, the CRISPR/Cas9 technique was used to establish c-Myb gene KO CRC cell lines. Cellular functional assays in vitro and in vivo were used to evaluate the impact of c-Myb KO in CRC cells. Finally, RNA sequencing was used to investigate the potential oncogenic mechanisms regulated by c-Myb in CRC progression and related cellular validations were accordingly carried out. As a result, c-Myb is significantly overexpressed in CRC tissues as compared with adjacent normal tissues. High expression of c-Myb is positively correlated with lymph node metastasis and poor prognosis. Univariate analysis and multivariate analysis further identify c-Myb as an independent unfavorable prognostic factor for CRC patients. c-Myb KO inhibits the proliferation, apoptosis resistance, invasion, metastasis, colony formation and in vivo tumorigenesis of CRC cells. Also, the mechanism investigation indicates that c-Myb may promote CRC progression by regulating c-fos. c-fos overexpression can rescue the inhibitory effect of c-Myb KO on the malignant characteristics of CRC cells. Finally, we find that c-Myb KO inhibits the epithelial-mesenchymal transition (EMT) molecular phenotype in CRC cells, whereas c-fos overexpression can rescue this inhibitory effect. This study suggests that c-Myb promotes the malignant progression of CRC through c-fos-induced EMT and has the potential to be a promising prognostic biomarker and therapeutic target.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
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Proteínas Proto-Oncogênicas c-fos
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Proteínas Proto-Oncogênicas c-myb
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article