RESUMEN

BACKGROUND: MiR-27a is significantly overexpressed in triple-negative breast cancer (TNBC). However, the exact biological function of MiR-27a in TNBC is not fully understood. In this study, we verified miR-27a expression in TNBC cells and explored how its overexpression modulates radiosensitivity of the cells. MATERIAL/METHODS: qRT-PCR analysis was performed to study miR-27a expression in TNBC lines MDA-MB-435 and MDA-MB-231 and in normal human breast epithelial cell line MCF10A. Dual luciferase assay was performed to verify a putative downstream target of miR-27a, CDC27. CCK-8 assay was used to assess the influence of miR-27a-CDC27 axis on cell proliferation under irradiation (IR) treatment. RESULTS: We confirmed significantly higher miR-27a expression in 2 TNBC cell lines--MDA-MB-435 and MDA-MB-231--than in human breast epithelial cell line MCF10A. miR-27a could modulate proliferation and radiosensitivity of TNBC cells. CDC-27 is a direct target of miR-27a and its downregulation conferred increased radioresistance of the cells. CONCLUSIONS: The miR-27a-CDC27 axis might play an important role in modulating response to radiotherapy in TNBC cells. Testing miR-27a expression might be a useful way to identify a subgroup of patients who will benefit from an IR-based therapeutic approach.

Asunto(s)

Subunidad Apc3 del Ciclosoma-Complejo Promotor de la Anafase/antagonistas & inhibidores , MicroARNs/fisiología , Proteínas de Neoplasias/antagonistas & inhibidores , Neoplasias de la Mama Triple Negativas/radioterapia , Subunidad Apc3 del Ciclosoma-Complejo Promotor de la Anafase/biosíntesis , Subunidad Apc3 del Ciclosoma-Complejo Promotor de la Anafase/genética , Subunidad Apc3 del Ciclosoma-Complejo Promotor de la Anafase/fisiología , Sitios de Unión , Mama/citología , Línea Celular Tumoral/efectos de la radiación , Células Cultivadas , Secuencia Conservada , Regulación hacia Abajo , Células Epiteliales/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células HEK293 , Humanos , Terapia Molecular Dirigida , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/fisiología , Oligonucleótidos/farmacología , Interferencia de ARN , ARN Interferente Pequeño/farmacología , Tolerancia a Radiación/genética , Proteínas Recombinantes de Fusión/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Ensayo de Tumor de Célula Madre