Expression of long non-coding RNA ENSG00000226738 (LncKLHDC7B) is enriched in the immunomodulatory triple-negative breast cancer subtype and its alteration promotes cell migration, invasion, and resistance to cell death
Por:
Beltrán-Anaya F.O., Romero-Cordoba, Sandra, Rebollar-Vega, Rosa, Arrieta, Oscar, Bautista-Pina, Veronica, Dominguez-Reyes, Carlos, Villegas-Carlos, Felipe, Tenorio-Torres, Alberto, Alfaro-Riuz, Luis, Jimenez-Morales, Silvia, Cedro-Tanda, Alberto, Rios-Romero, Magdalena, Reyes-Grajeda J.P., Tagliabue, Elda, Iorio, V, Marilena, Hidalgo-Miranda, Alfredo
Publicada:
1 ene 2019
Resumen:
Triple negative breast cancer (TNBC) represents an aggressive phenotype with poor prognosis compared with ER, PR, and HER2-positive tumors. TNBC is a heterogeneous disease, and gene expression analysis has identified seven molecular subtypes. Accumulating evidence demonstrates that long non-coding RNA (lncRNA) are involved in regulation of gene expression and cancer biology, contributing to essential cancer cell functions. In this study, we analyzed the expression profile of lncRNA in TNBC subtypes from 156 TNBC samples, and then characterized the functional role of LncKLHDC7B (ENSG00000226738). A total of 710 lncRNA were found to be differentially expressed between TNBC subtypes, and a subset of these altered lncRNA were independently validated. We discovered that LncKLHDC7B (ENSG00000226738) acts as a transcriptional modulator of its neighboring coding gene KLHDC7B in the immunomodulatory subtype. Furthermore, LncKLHDC7B knockdown enhanced migration and invasion, and promoted resistance to cellular death. Our findings confirmed the contribution of LncKLHDC7B to induction of apoptosis and inhibition of cell migration and invasion, suggesting that TNBC tumors with enrichment of LncKLHDC7B may exhibit distinct regulatory activity, or that this may be a generalized process in breast cancer. Additionally, in silico analysis confirmed for the first time that the low expression of KLHDC7B and LncKLHDC7B is associated with poor prognosis in patients with breast cancer. © 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
Filiaciones:
Beltrán-Anaya F.O.:
Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Programa de Doctorado en Ciencias Biomédicas, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico
Romero-Cordoba, Sandra:
Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Department of Experimental Oncology and Molecular Medicine, Istituto Nazionale dei Tumori, Milan, Italy
Inst Nacl Med Genom, Lab Genom Canc, Mexico City, DF, Mexico
Iorio, Marilena, V, Ist Nazl Tumori, Dept Expt Oncol & Mol Med, Milan, Italy
Rebollar-Vega, Rosa:
Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Inst Nacl Med Genom, Lab Genom Canc, Mexico City, DF, Mexico
Arrieta, Oscar:
Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), México City, Mexico
Inst Nacl Cancerol INCen, Thorac Oncol Unit, Mexico City, DF, Mexico
Bautista-Pina, Veronica:
Instituto de Enfermedades de la Mama FUCAM, Mexico City, Mexico
Inst Enfermedades Mama FUCAM, Mexico City, DF, Mexico
Dominguez-Reyes, Carlos:
Instituto de Enfermedades de la Mama FUCAM, Mexico City, Mexico
Inst Enfermedades Mama FUCAM, Mexico City, DF, Mexico
Villegas-Carlos, Felipe:
Instituto de Enfermedades de la Mama FUCAM, Mexico City, Mexico
Inst Enfermedades Mama FUCAM, Mexico City, DF, Mexico
Tenorio-Torres, Alberto:
Instituto de Enfermedades de la Mama FUCAM, Mexico City, Mexico
Inst Enfermedades Mama FUCAM, Mexico City, DF, Mexico
Alfaro-Riuz, Luis:
Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Inst Nacl Med Genom, Lab Genom Canc, Mexico City, DF, Mexico
Jimenez-Morales, Silvia:
Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Inst Nacl Med Genom, Lab Genom Canc, Mexico City, DF, Mexico
Cedro-Tanda, Alberto:
Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Programa de Doctorado en Ciencias Biomédicas, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico
Inst Nacl Med Genom, Lab Genom Canc, Mexico City, DF, Mexico
Univ Nacl Autonoma Mexico, Fac Med, Programa Doctorado Ciencias Biomed, Mexico City, DF, Mexico
Rios-Romero, Magdalena:
Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Inst Nacl Med Genom, Lab Genom Canc, Mexico City, DF, Mexico
Reyes-Grajeda J.P.:
Unidad de Proteómica Médica, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Tagliabue, Elda:
Department of Experimental Oncology and Molecular Medicine, Istituto Nazionale dei Tumori, Milan, Italy
Iorio, Marilena, V, Ist Nazl Tumori, Dept Expt Oncol & Mol Med, Milan, Italy
Iorio, V, Marilena:
Department of Experimental Oncology and Molecular Medicine, Istituto Nazionale dei Tumori, Milan, Italy
Hidalgo-Miranda, Alfredo:
Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Inst Nacl Med Genom, Lab Genom Canc, Mexico City, DF, Mexico
Inst Nacl Med Genom, Unidad Proteom Med, Mexico City, DF, Mexico
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