A novel miR-200c/c-myc negative regulatory feedback loop is essential to the EMT process, CSC biology and drug sensitivity in nasopharyngeal cancer.
Exp Cell Res
; 391(2): 111817, 2020 06 15.
Article
em En
| MEDLINE
| ID: mdl-32179097
ABSTRACT
Overexpression of the c-Myc oncogene has been implicated in cancer stem cell - like (CSC) phenotypes and epithelial-to-mesenchymal transition (EMT) in cancer. However, the underlying molecular mechanism by which c-Myc regulates EMT and CSC potential in remains unclear. In the present study, we showed that the expression of c-Myc protein is inversely correlated with microRNA (miR)-200c expression in primary tumor samples from nasopharyngeal cancer (NPC) patients. We further demonstrated that Myc and miR-200c negatively regulate the expression each other in NPC cell lines. c-Myc transcriptionally repressed expression of miR-200c by directly binding to two E-box sites located within a 1 kb segment upstream of TSS of the miR-200c. In addition, miR-200c post-transcriptionally repressed expression of c-Myc by binding to its 3'-untranslated region, suggesting the existence of a negative feedback loop between Myc and miR-200c. Overexpression of c-Myc interfered with this feedback loop and activated the EMT program, induced CSC phenotypes, and enhanced drug sensitivity, whereas miR-200c could counteract these biological effects of c-Myc. Our results provide a novel mechanism governing c-Myc and miR-200c expression and indicate that either targeting c-Myc or restoring miR-200c expression would be a promising approach to overcome oncogenic role of c-Myc in NPC.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Neoplásicas
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Regulação Neoplásica da Expressão Gênica
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Neoplasias Nasofaríngeas
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Proteínas Proto-Oncogênicas c-myc
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Resistencia a Medicamentos Antineoplásicos
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MicroRNAs
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Transição Epitelial-Mesenquimal
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Exp Cell Res
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China