TY - JOUR
T1 - Role of RUNX2 transcription factor in epithelial mesenchymal transition in non-small cell lung cancer lung cancer
T2 - Epigenetic control of the RUNX2 P1 promoter
AU - Herreño, Angélica María
AU - Ramírez, Andrea Carolina
AU - Chaparro, Viviana Paola
AU - Fernandez, María José
AU - Cañas, Alejandra
AU - Morantes, Carlos Fabian
AU - Moreno, Olga María
AU - Brugés, Ricardo Elias
AU - Mejía, Juan Andrés
AU - Bustos, Fernando José
AU - Montecino, Martín
AU - Rojas, Adriana P.
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by grants from Pontificia Universidad Javeriana (PUJ) (6276, PUJ 7189) and M.M. was supported by FONDAP (15090007) and CONICYT-REDES (150109). A.M.H. was supported by COLCIENCIAS grant no. 705.2015-Jóvenes Investigadores e innovadores 2015.
Publisher Copyright:
© The Author(s) 2019.
PY - 2019/5/1
Y1 - 2019/5/1
N2 - 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-β 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.
AB - 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-β 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.
KW - epigenetic
KW - epithelial mesenchymal transition
KW - histone
KW - lung cancer
KW - RUNX2
UR - http://www.scopus.com/inward/record.url?scp=85066436930&partnerID=8YFLogxK
U2 - 10.1177/1010428319851014
DO - 10.1177/1010428319851014
M3 - Article
C2 - 31109257
AN - SCOPUS:85066436930
SN - 1010-4283
VL - 41
JO - Tumor Biology
JF - Tumor Biology
IS - 5
ER -
