NDLI: Overexpression of MEOX2 and TWIST1 Is Associated with H3K27me3 Levels and Determines Lung Cancer Chemoresistance and Prognosis

Content Provider	PubMed Central
Author	Ávila-moreno, Federico Leonel, Armas-lópez Álvarez-moran, Aldo M. López-bujanda, Zoila Blanca, Ortiz-quintero Alfredo, Hidalgo-miranda Francisco, Urrea-ramírez María, Rivera-rosales R. Eugenia, Vázquez-manríquez Peña-mirabal, Erika José, Morales-gómez Vázquez-minero, Juan C. Téllez-becerra, José L. Roberto, Ramírez-mendoza Ávalos-bracho, Alejandro Alba, Enrique Guzmán De Karla, Vázquez-santillán Vilma, Maldonado-lagunas Patricio, Santillán-doherty Patricia, Piña-sánchez Joaquin, Zúñiga-ramos
Editor	Patnaik, Santosh
Copyright Year	2014
Abstract	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.
Related Links	http://dx.doi.org/10.1371/journal.pone.0114104
Starting Page	114104
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	12
Volume Number	9
Language	English
Publisher	Public Library of Science
Publisher Date	2014-12-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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Correction: Overexpression of MEOX2 and TWIST1 is Associated with H3K27me3 Levels and Determines Lung Cancer Chemoresistance and Prognosis

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Correction: Overexpression of MEOX2 and TWIST1 is Associated with H3K27me3 Levels and Determines Lung Cancer Chemoresistance and Prognosis

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