دورية أكاديمية
أعرض في EDS

Overexpression of MEOX2 and TWIST1 is associated with H3K27me3 levels and determines lung cancer chemoresistance and prognosis.

التفاصيل البيبلوغرافية
العنوان: Overexpression of MEOX2 and TWIST1 is associated with H3K27me3 levels and determines lung cancer chemoresistance and prognosis.
المؤلفون: Ávila-Moreno F; Universidad Nacional Autónoma de México (UNAM), Facultad de Estudios Superiores (FES)-Iztacala, Biomedicine Research Unit (UBIMED), Cancer Epigenomics Laboratory 12, Tlalnepantla, Mexico State, Mexico; Instituto Nacional de Enfermedades Respiratorias (INER), Mexico City, Mexico., Armas-López L; Universidad Nacional Autónoma de México (UNAM), Facultad de Estudios Superiores (FES)-Iztacala, Biomedicine Research Unit (UBIMED), Cancer Epigenomics Laboratory 12, Tlalnepantla, Mexico State, Mexico., Álvarez-Moran AM; Instituto Nacional de Enfermedades Respiratorias (INER), Mexico City, Mexico., López-Bujanda Z; Universidad Nacional Autónoma de México (UNAM), Facultad de Estudios Superiores (FES)-Iztacala, Biomedicine Research Unit (UBIMED), Cancer Epigenomics Laboratory 12, Tlalnepantla, Mexico State, Mexico; Instituto Nacional de Enfermedades Respiratorias (INER), Mexico City, Mexico; Johns Hopkins University, Medical Institutions, Maryland, Baltimore, United States of America., Ortiz-Quintero B; Instituto Nacional de Enfermedades Respiratorias (INER), Mexico City, Mexico., Hidalgo-Miranda A; Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico., Urrea-Ramírez F; Instituto Nacional de Enfermedades Respiratorias (INER), Mexico City, Mexico., Rivera-Rosales RM; Instituto Nacional de Enfermedades Respiratorias (INER), Mexico City, Mexico., Vázquez-Manríquez E; Instituto Nacional de Enfermedades Respiratorias (INER), Mexico City, Mexico., Peña-Mirabal E; Instituto Nacional de Enfermedades Respiratorias (INER), Mexico City, Mexico., Morales-Gómez J; Instituto Nacional de Enfermedades Respiratorias (INER), Mexico City, Mexico., Vázquez-Minero JC; Instituto Nacional de Enfermedades Respiratorias (INER), Mexico City, Mexico., Téllez-Becerra JL; Instituto Nacional de Enfermedades Respiratorias (INER), Mexico City, Mexico., Ramírez-Mendoza R; Universidad Nacional Autónoma de México (UNAM), Facultad de Estudios Superiores (FES)-Iztacala, Biomedicine Research Unit (UBIMED), Cancer Epigenomics Laboratory 12, Tlalnepantla, Mexico State, Mexico., Ávalos-Bracho A; Instituto Nacional de Enfermedades Respiratorias (INER), Mexico City, Mexico., de Alba EG; Instituto Nacional de Enfermedades Respiratorias (INER), Mexico City, Mexico., Vázquez-Santillán K; Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico., Maldonado-Lagunas V; Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico., Santillán-Doherty P; Instituto Nacional de Enfermedades Respiratorias (INER), Mexico City, Mexico., Piña-Sánchez P; Unidad de Investigación Médica en Enfermedades Oncológicas (UIMEO), Instituto Mexicano del Seguro Social (IMSS), Centro Médico Nacional (CMN), Siglo XXI, México City, México., Zúñiga-Ramos J; Instituto Nacional de Enfermedades Respiratorias (INER), Mexico City, Mexico.
المصدر: PloS one [PLoS One] 2014 Dec 02; Vol. 9 (12), pp. e114104. Date of Electronic Publication: 2014 Dec 02 (Print Publication: 2014).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Carcinoma, Non-Small-Cell Lung/*drug therapy , Drug Resistance, Neoplasm/*genetics , Histones/*metabolism , Homeodomain Proteins/*genetics , Lung Neoplasms/*drug therapy , Nuclear Proteins/*genetics , Twist-Related Protein 1/*genetics, Adult ; Aged ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/pathology ; Chromosome Aberrations ; Chromosomes, Human, Pair 7 ; DNA Methylation ; Female ; Humans ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Male ; Middle Aged ; Prognosis
مستخلص: Lung cancer is the leading cause of death from malignant diseases worldwide, with the non-small cell (NSCLC) subtype accounting for the majority of cases. NSCLC is characterized by frequent genomic imbalances and copy number variations (CNVs), but the epigenetic aberrations that are associated with clinical prognosis and therapeutic failure remain not completely identify. In the present study, a total of 55 lung cancer patients were included and we conducted genomic and genetic expression analyses, immunohistochemical protein detection, DNA methylation and chromatin immunoprecipitation assays to obtain genetic and epigenetic profiles associated to prognosis and chemoresponse of NSCLC patients. Finally, siRNA transfection-mediated genetic silencing and cisplatinum cellular cytotoxicity assays in NSCLC cell lines A-427 and INER-37 were assessed to describe chemoresistance mechanisms involved. Our results identified high frequencies of CNVs (66-51% of cases) in the 7p22.3-p21.1 and 7p15.3-p15.2 cytogenetic regions. However, overexpression of genes, such as MEOX2, HDAC9, TWIST1 and AhR, at 7p21.2-p21.1 locus occurred despite the absence of CNVs and little changes in DNA methylation. In contrast, the promoter sequences of MEOX2 and TWIST1 displayed significantly lower/decrease in the repressive histone mark H3K27me3 and increased in the active histone mark H3K4me3 levels. Finally these results correlate with poor survival in NSCLC patients and cellular chemoresistance to oncologic drugs in NSCLC cell lines in a MEOX2 and TWIST1 overexpression dependent-manner. In conclusion, we report for the first time that MEOX2 participates in chemoresistance irrespective of high CNV, but it is significantly dependent upon H3K27me3 enrichment probably associated with aggressiveness and chemotherapy failure in NSCLC patients, however additional clinical studies must be performed to confirm our findings as new probable clinical markers in NSCLC patients.
التعليقات: Erratum in: PLoS One. 2016;11(2):e0146569. (PMID: 26863441)
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سلسلة جزيئية: GEO GSE62407
المشرفين على المادة: 0 (Histones)
0 (Homeodomain Proteins)
0 (MEOX2 protein, human)
0 (Nuclear Proteins)
0 (TWIST1 protein, human)
0 (Twist-Related Protein 1)
تواريخ الأحداث: Date Created: 20141203 Date Completed: 20160108 Latest Revision: 20220330
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC4252097
DOI: 10.1371/journal.pone.0114104
PMID: 25460568
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0114104