miR-196b-5p Regulates Colorectal Cancer Cell Migration and Metastases through Interaction with HOXB7 and GALNT5.
Clin Cancer Res
; 23(17): 5255-5266, 2017 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-28533224
ABSTRACT
Purpose:
miR-196b-5p has been previously implicated in malignant transformation; however, its role in colorectal cancer has not been fully explored. In this study, we examine the clinical and biological relevance of miR-196b-5p, and the molecular pathways regulated by miR-196b-5p in colorectal cancer.ExperimentalDesign:
miR-196b-5p expression was quantitated by qRT-PCR in 2 independent cohorts composed of 292 patients with colorectal cancer in total, to explore its biomarker potential. Transient and stable gain- and loss-of-function experiments were conducted in a panel of colorectal cancer cell lines and mice, to evaluate the impact of miR-196b-5p on proliferation, chemosensitivity, migration/invasion, and metastases formation in vitro and in vivo The molecular pathways influenced by miR-196b-5p were characterized using whole transcriptome profiling, in silico target prediction tools, luciferase interaction assays, and phenocopy/rescue gene knockdown experiments.Results:
Low miR-196b-5p expression was significantly associated with metastases and poor outcomes in 2 independent colorectal cancer patient cohorts (P < 0.05, log-rank test). miR-196b-5p inhibition led to significantly increased colorectal cancer cell migration/invasion and metastases formation in mice, whereas ectopic overexpression showed the opposite phenotype. Molecular profiling and target confirmation identified an interaction between miR-196b-5p and HOXB7 and GALNT5, which in turn regulated colorectal cancer cell migration.Conclusions:
The association of low levels of miR-196b-5p and poor prognosis in patients with colorectal cancer can be explained by its influence on cancer cell migration and metastases formation. miR-196b-5p has an impact on colorectal cancer progression pathways through direct interaction with genes involved in cancer cell migration. Clin Cancer Res; 23(17); 5255-66. ©2017 AACR.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
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N-Acetilgalactosaminiltransferases
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Proteínas de Homeodomínio
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MicroRNAs
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Aged
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Aged80
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Cancer Res
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Áustria