Tumor suppressor miR-29c regulates radioresistance in lung cancer cells
Por:
Arechaga-Ocampo E., Lopez-Camarillo C., Villegas-Sepulveda N., Gonzalez-De la Rosa C.H., Perez-Añorve I.X., Roldan-Perez R., Flores-Perez A., Pena-Curiel, Omar, Angeles-Zaragoza O., Rangel Corona R., Gonzalez-Barrios J.A., Bonilla-Moreno R., del Moral-Hernandez O., Herrera L.A., Garcia-Carranca A.
Publicada:
1 mar 2017
Resumen:
Radiotherapy is an important treatment option for non-small cell lung
carcinoma patients. Despite the appropriate use of radiotherapy,
radioresistance is a biological behavior of cancer cells that limits the
efficacy of this treatment. Deregulation of microRNAs contributes to the
molecular mechanism underlying resistance to radiotherapy in cancer
cells. Although the functional roles of microRNAs have been well
described in lung cancer, their functional roles in radioresistance are
largely unclear. In this study, we established a non-small cell lung
carcinoma Calu-1 radioresistant cell line by continuous exposure to
therapeutic doses of ionizing radiation as a model to investigate
radioresistance-associated microRNAs. Our data show that 50 microRNAs
were differentially expressed in Calu-1 radioresistant cells (16
upregulated and 34 downregulated); furthermore, well-known and novel
microRNAs associated with resistance to radiotherapy were identified.
Gene ontology and enrichment analysis indicated that modulated microRNAs
might regulate signal transduction, cell survival, and apoptosis.
Accordingly, Calu-1 radioresistant cells were refractory to radiation by
increasing cell survival and reducing the apoptotic response. Among
deregulated microRNAs, miR-29c was significantly suppressed.
Reestablishment of miR-29c expression in Calu-1 radioresistant cells
overcomes the radioresistance through the activation of apoptosis and
downregulation of Bcl-2 and Mcl-1 target genes. Analysis of The Cancer
Genome Atlas revealed that miR-29c is also suppressed in tumor samples
of non-small cell lung carcinoma patients. Notably, we found that low
miR-29c levels correlated with shorter relapse-free survival of
non-small cell lung carcinoma patients treated with radiotherapy.
Together, these results indicate a new role of miR-29c in
radioresistance, highlighting their potential as a novel biomarker for
outcomes of radiotherapy in lung cancer.
Filiaciones:
Arechaga-Ocampo E.:
Univ Autonoma Metropolitana, Dept Ciencias Nat, Unidad Cuajimalpa, Av Vasco de Quiroga 4871, Mexico City 05348, DF, Mexico
Departamento de Ciencias Naturales, Universidad Autónoma Metropolitana, Unidad Cuajimalpa, México City, Mexico
Lopez-Camarillo C.:
Univ Autonoma Ciudad Mexico, Posgrad Ciencias Genom, Mexico City, DF, Mexico
Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, Mexico City, Mexico
Villegas-Sepulveda N.:
Ctr Invest & Estudios Avanzados CINVESTAV, Dept Biomed Mol, Mexico City, DF, Mexico
Departamento de Biomedicina Molecular, Centro de Investigacion y de Estudios Avanzados (CINVESTAV), Mexico City, Mexico
Gonzalez-De la Rosa C.H.:
Univ Autonoma Metropolitana, Dept Ciencias Nat, Unidad Cuajimalpa, Av Vasco de Quiroga 4871, Mexico City 05348, DF, Mexico
Departamento de Ciencias Naturales, Universidad Autónoma Metropolitana, Unidad Cuajimalpa, México City, Mexico
Perez-Añorve I.X.:
Univ Autonoma Metropolitana, Dept Ciencias Nat, Unidad Cuajimalpa, Av Vasco de Quiroga 4871, Mexico City 05348, DF, Mexico
Departamento de Ciencias Naturales, Universidad Autónoma Metropolitana, Unidad Cuajimalpa, México City, Mexico
Roldan-Perez R.:
Univ Autonoma Metropolitana, Dept Ciencias Nat, Unidad Cuajimalpa, Av Vasco de Quiroga 4871, Mexico City 05348, DF, Mexico
Departamento de Ciencias Naturales, Universidad Autónoma Metropolitana, Unidad Cuajimalpa, México City, Mexico
Flores-Perez A.:
Univ Autonoma Ciudad Mexico, Posgrad Ciencias Genom, Mexico City, DF, Mexico
Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, Mexico City, Mexico
Pena-Curiel, Omar:
Inst Nacl Cancerol, Dept Oncol Med, Mexico City, DF, Mexico
Angeles-Zaragoza O.:
Inst Nacl Cancerol, Unidad Radioterapia, Mexico City, DF, Mexico
Unidad de Radioterapia, Instituto Nacional de Cancerologia, Mexico City, Mexico
Rangel Corona R.:
Univ Nacl Autonoma Mexico, FES Zaragoza, UMIEZ, Lab Oncol Celular, Mexico City, DF, Mexico
Laboratorio de Oncologia Celular, UMIEZ, FES Zaragoza, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City, Mexico
Gonzalez-Barrios J.A.:
Hosp Reg 1 Octubre, Lab Med Genom, Mexico City, DF, Mexico
Laboratorio de Medicina Genomica, Hospital Regional 1º de Octubre, Mexico City, Mexico
Bonilla-Moreno R.:
Ctr Invest & Estudios Avanzados CINVESTAV, Dept Biomed Mol, Mexico City, DF, Mexico
Departamento de Biomedicina Molecular, Centro de Investigacion y de Estudios Avanzados (CINVESTAV), Mexico City, Mexico
del Moral-Hernandez O.:
Univ Autonoma Guerrero, Unidad Acad Ciencias Quim Biol, Lab Biomed Mol, Chilpancingo, Mexico
Laboratorio de Biomedicina Molecular, Unidad Academica de Ciencias Quimico Biologicas, Universidad Autonoma de Guerrero, Chilpancingo, Mexico
Herrera L.A.:
Univ Nacl Autonoma Mexico, Inst Nacl Cancerol, Unidad Invest Biomed Canc, Mexico City, DF, Mexico
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mexico City, DF, Mexico
Unidad de Investigacion Biomedica en Cancer, Instituto Nacional de Cancerologia and Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City, Mexico
Garcia-Carranca A.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mexico City, DF, Mexico
Univ Nacl Autonoma Mexico, Lab Virus & Canc, Unidad Invest Biomed Canc, Inst Nacl Cancerol, Mexico City, DF, Mexico
Unidad de Investigacion Biomedica en Cancer, Instituto Nacional de Cancerologia and Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City, Mexico
Laboratorio de Virus y Cancer, Unidad de Investigacion Biomedica en Cancer, Instituto Nacional de Cancerologia and Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City, Mexico
Departamento de Oncología Medica, Instituto Nacional de Cancerologia, Mexico City, Mexico
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