Role of the transcription factor RUNX2 in the Transition epithelium mesenchyme EMT in lung cancer NSCLC

AbstractLung cancer has a high mortality rate worldwide in both men and women. About 15% of patients diagnosed with this type of cancer do not have a survival greater than 5 years, given that it is diagnosed in advanced stages where it may be affected to other tissues or organs. In recent years the participation of transcription factors (TF) specific lineage in the tumor progression of a variety of cancer types has been reported. One of the FT that can participate in cancer is Runx2 the master gene of early and late osteogenic differentiation. In thyroid and prostate cancer, it has been reported that Runx2 regulates the expression of genes that participate in the process of mobility and invasion of tumor cells. In this study we report an over-expression of Runx2 in 16 patients with primary NSCLC and / or metastatic lung cancer that is related to the enrichment of H3K27Ac in the P1 promoter of the gene. In some of the patients analyzed, we also detected enrichment in H3K4Me3 and recruitment of enzymes Wdr5, Mll2, Mll4 and UTX, members of the COMPASS-LIKE complex. Additionally, we demonstrated the role of Runx2 in the mesenchymal epithelial transition process EMT, by performing tests of loss of function of the gene in the lung adenocarcinoma cell line A549. We show that Runx2 participates in the transcriptional regulation of E-cadherin, Vimentin, Snail and Twist affecting the EMT process; which is reflected in the decrease in the migratory capacity of lung adenocarcinoma cells. Our results identify Runx2 as a key component that controls EMT process.Key words: Runx2, Mesenchymal epithelium-EMT transition, lung cancer, transcription factor.