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Oncotarget ; 6(14): 12558-73, 2015 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-25940441

RESUMO

Stem cell marker, Musashi-1 (MSI1) is over-expressed in many cancer types; however the molecular mechanisms involved in MSI1 over-expression are not well understood. We investigated the microRNA (miRNA) regulation of MSI1 and the implications this regulation plays in colorectal cancer. MicroRNA miR-137 was identified as a MSI1-targeting microRNA by immunoblotting and luciferase reporter assays. MSI1 protein was found to be highly expressed in 79% of primary rectal tumors (n=146), while miR-137 expression was decreased in 84% of the rectal tumor tissues (n=68) compared to paired normal mucosal samples. In addition to reduced MSI1 protein, exogenous expression of miR-137 inhibited cell growth, colony formation, and tumorsphere growth of colon cancer cells. Finally, in vivo studies demonstrated that induction of miR-137 can decrease growth of human colon cancer xenografts. Our results demonstrate that miR-137 acts as a tumor-suppressive miRNA in colorectal cancers and negatively regulates oncogenic MSI1.


Assuntos
Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/genética , Proteínas do Tecido Nervoso/genética , Proteínas de Ligação a RNA/genética , Animais , Western Blotting , Neoplasias Colorretais/patologia , Progressão da Doença , Genes Supressores de Tumor , Células HCT116 , Xenoenxertos , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Nus , Proteínas do Tecido Nervoso/biossíntese , Proteínas de Ligação a RNA/biossíntese , Reação em Cadeia da Polimerase em Tempo Real , Análise Serial de Tecidos
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