New insights into radioresistance in breast cancer identify a dual function of miR-122 as a tumor suppressor and oncomiR
Por:
Perez-Añorve I.X., Gonzalez-De la Rosa C.H., Soto-Reyes E., Beltran-Anaya F.O., Del Moral-Hernandez O., Salgado-Albarran M., Angeles-Zaragoza O., Gonzalez-Barrios J.A., Landero-Huerta D.A., Chavez-Saldaña M., Garcia-Carranca A., Villegas-Sepulveda N., Arechaga-Ocampo E.
Publicada:
1 ene 2019
Resumen:
Radioresistance of tumor cells gives rise to local recurrence and disease progression in many patients. MicroRNAs (miRNAs) are master regulators of gene expression that control oncogenic pathways to modulate the radiotherapy response of cells. In the present study, differential expression profiling assays identified 16 deregulated miRNAs in acquired radioresistant breast cancer cells, of which miR-122 was observed to be up-regulated. Functional analysis revealed that miR-122 has a role as a tumor suppressor in parental cells by decreasing survival and promoting radiosensitivity. However, in radioresistant cells, miR-122 functions as an oncomiR by promoting survival. The transcriptomic landscape resulting from knockdown of miR-122 in radioresistant cells showed modulation of the ZNF611, ZNF304, RIPK1, HRAS, DUSP8 and TNFRSF21 genes. Moreover, miR-122 and the set of affected genes were prognostic factors in breast cancer patients treated with radiotherapy. Our data indicate that up-regulation of miR-122 promotes cell survival in acquired radioresistant breast cancer and also suggest that miR-122 differentially controls the response to radiotherapy by a dual function as a tumor suppressor an and oncomiR dependent on cell phenotype. © 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
Filiaciones:
Perez-Añorve I.X.:
Posgrado en Ciencias Naturales e Ingenieria, Division de Ciencias Naturales e Ingenieria, Universidad Autonoma Metropolitana, Mexico City, Mexico
Departamento de Ciencias Naturales, Universidad Autónoma Metropolitana, Unidad Cuajimalpa, México City, Mexico
Gonzalez-De la Rosa C.H.:
Departamento de Ciencias Naturales, Universidad Autónoma Metropolitana, Unidad Cuajimalpa, México City, Mexico
Soto-Reyes E.:
Departamento de Ciencias Naturales, Universidad Autónoma Metropolitana, Unidad Cuajimalpa, México City, Mexico
Beltran-Anaya F.O.:
Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Del Moral-Hernandez O.:
Laboratorio de Virologia y Epigenetica del Cancer, Facultad de Ciencias Quimico Biologicas, Universidad Autonoma de Guerrero, Chilpancingo, Mexico
Salgado-Albarran M.:
Departamento de Ciencias Naturales, Universidad Autónoma Metropolitana, Unidad Cuajimalpa, México City, Mexico
Angeles-Zaragoza O.:
Unidad de Radioterapia, Instituto Nacional de Cancerologia, Mexico City, Mexico
Gonzalez-Barrios J.A.:
Laboratorio de Medicina Genomica, Hospital Regional “1° de Octubre”, Mexico City, Mexico
Landero-Huerta D.A.:
Posgrado en Ciencias Naturales e Ingenieria, Division de Ciencias Naturales e Ingenieria, Universidad Autonoma Metropolitana, Mexico City, Mexico
Departamento de Ciencias Naturales, Universidad Autónoma Metropolitana, Unidad Cuajimalpa, México City, Mexico
Laboratorio de Biología de la Reproducción, Instituto Nacional de Pediatría, Mexico City, Mexico
Chavez-Saldaña M.:
Laboratorio de Biología de la Reproducción, Instituto Nacional de Pediatría, Mexico City, Mexico
Garcia-Carranca A.:
Unidad de Investigacion Biomedica en Cancer-Laboratorio de Virus y Cancer, Instituto Nacional de Cancerologia, Mexico City, Mexico
Villegas-Sepulveda N.:
Departamento de Biomedicina Molecular, Centro de Investigacion y de Estudios Avanzados (CINVESTAV), Mexico City, Mexico
Arechaga-Ocampo E.:
Departamento de Ciencias Naturales, Universidad Autónoma Metropolitana, Unidad Cuajimalpa, México City, Mexico
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