1. Role of RUNX2 transcription factor in epithelial mesenchymal transition in non-small cell lung cancer lung cancer: Epigenetic control of the RUNX2 P1 promoter
- Author
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Carlos Fabian Morantes, Ricardo Elias Brugés, María José Fernández, Andrea Carolina Ramírez, Juan Andres Mejia, Viviana Paola Chaparro, Fernando J. Bustos, Adriana Rojas, Alejandra Cañas, Martin Montecino, Olga Moreno, and Angélica Herreño
- Subjects
WDR5 protein ,Male ,Secondary ,Lung Neoplasms ,Gene control ,Apoptosis ,Core Binding Factor Alpha 1 Subunit ,Cancer growth ,Gene overexpression ,Twist transcription factor ,0302 clinical medicine ,Cell Movement ,Pathology ,Tumor Cells, Cultured ,Transcription factor Snail1 ,Cell proliferation ,Gene expression regulation ,Aged, 80 and over ,Histone H3 ,Messenger RNA ,VIMENTIN gene ,Correlation analysis ,Cell motion ,General Medicine ,Prognosis ,Gene Expression Regulation, Neoplastic ,Enrichment culture ,030220 oncology & carcinogenesis ,Adenocarcinoma ,Epigenetics ,Lung cancer ,MLL2 protein ,Human ,Clinical article ,RUNX2 ,Case control study ,P57 gene ,Article ,Tumor cell culture ,03 medical and health sciences ,Genetics ,Vimentin ,Humans ,Tumor marker ,Lung tumor ,Aged ,Very elderly ,Twist related protein 1 ,Follow up ,UTX protein ,medicine.disease ,030104 developmental biology ,Human cell ,Enzyme ,Case-Control Studies ,Non small cell lung cancer ,Lung adenocarcinoma cell line ,0301 basic medicine ,Unclassified drug ,Gene loss ,Transcription factor RUNX2 ,Epigenesis, Genetic ,Prostate cancer ,TWIST1 gene ,Carcinoma, Non-Small-Cell Lung ,RUNX2 gene ,SNAIL1 gene ,Middle aged ,Promoter Regions, Genetic ,Priority journal ,Genetic epigenesis ,RUNX2 protein, human ,MLL4 protein ,Promoter region ,Epigenetic ,Transcription regulation ,Middle Aged ,Histone ,Lung metastasis ,A-549 cell line ,Lung carcinogenesis ,Female ,Adult ,Epithelial-Mesenchymal Transition ,Tumor invasion ,Biology ,medicine ,Biomarkers, Tumor ,Cell migration ,Neoplasm Invasiveness ,Epithelial–mesenchymal transition ,Human tissue ,Transcription factor ,Cell Proliferation ,Gene knockdown ,Cancer ,COMPASS LIKE complex ,Metabolism ,Genetic association ,biology.protein ,Cancer research ,Transforming growth factor beta ,Epithelial mesenchymal transition ,Controlled study ,Gene function ,Follow-Up Studies - Abstract
Lung cancer has a high mortality rate in men and women worldwide. Approximately 15% of diagnosed patients with this type of cancer do not exceed the 5-year survival rate. Unfortunately, diagnosis is established in advanced stages, where other tissues or organs can be affected. In recent years, lineage-specific transcription factors have been associated with a variety of cancers. One such transcription factor possibly regulating cancer is RUNX2, the master gene of early and late osteogenesis. In thyroid and prostate cancer, it has been reported that RUNX2 regulates expression of genes important in tumor cell migration and invasion. In this study, we report on RUNX2/p57 overexpression in 16 patients with primary non-small cell lung cancer and/or metastatic lung cancer associated with H3K27Ac at P1 gene promoter region. In some patients, H3K4Me3 enrichment was also detected, in addition to WDR5, MLL2, MLL4, and UTX enzyme recruitment, members of the COMPASS-LIKE complex. Moreover, transforming growth factor-? induced RUNX2/p57 overexpression and specific RUNX2 knockdown supported a role for RUNX2 in epithelial mesenchymal transition, which was demonstrated through loss of function assays in adenocarcinoma A549 lung cancer cell line. Furthermore, RUNX2 increased expression of epithelial mesenchymal transition genes VIMENTIN, TWIST1, and SNAIL1, which reflected increased migratory capacity in lung adenocarcinoma cells. © The Author(s) 2019.
- Published
- 2019