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Cell Cycle ; 19(2): 233-245, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31876226

RESUMO

Background: Homeobox B5 (HOXB5) is associated with the poor prognosis of various cancer types. However, the specific mechanism by which HOXB5 promotes the malignant progression of pancreatic cancer (PC) remains to be determined.Methods: The Cancer Genome Atlas database indicated HOXB5 expression level correlated to PC prognosis. The biological functions of HOXB5 was confirmed by colony formation, migration, and invasion assays. The effects of HOXB5 on the expression of cancer stem cell and epithelial-mesenchymal transition markers were evaluated. The downstream target of HOXB5 was miR-6723, which was detected by transcriptional assay. A xenograft tumor model was established in nude mice for the assessment of the role of HOXB5 in tumor growth and metastasis.Results: PC tissues had higher HOXB5 expression levels than noncancerous tissues, and high HOXB5 expression was significantly associated with poor PC prognosis. HOXB5 knockdown suppressed clone formation and the proliferation, invasion, and migration of PC cells in vitro. Conversely, these activities were enhanced by HOXB5 overexpression. The HOXB5 that bound two synergy motifs regulated miR-6723 expression and contributed to PC malignant progression. The role of HOXB5 in promoting tumor growth and metastasis was verified in vivo. Further investigation revealed that Twist1 and Zeb1 expression levels were increased by HOXB5.Conclusions: HOXB5 overexpression was significantly correlated with poor PC prognosis. HOXB5 accelerated the malignant progression of PC by up-regulating miR-6723, which afforded PC cells stem-like properties and facilitated the epithelial-mesenchymal transition of PC cells.


Assuntos
Progressão da Doença , Proteínas de Homeodomínio/metabolismo , MicroRNAs/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Transdução de Sinais , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Sequência Conservada/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , Humanos , Camundongos Nus , MicroRNAs/genética , Invasividade Neoplásica , Metástase Neoplásica , Motivos de Nucleotídeos/genética , Prognóstico , Regiões Promotoras Genéticas/genética , Ligação Proteica , Regulação para Cima/genética
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