Role of RUNX2 transcription factor in epithelial mesenchymal transition in non-small cell lung cancer lung cancer

Epigenetic control of the RUNX2 P1 promoter

Angélica María Herreño, Andrea Carolina Ramírez, Viviana Paola Chaparro, María José Fernandez, Alejandra Cañas, Carlos Fabian Morantes, Olga María Moreno, Ricardo Elias Brugés, Juan Andrés Mejía, Fernando José Bustos, Martín Montecino, Adriana P. Rojas

Resultado de la investigación: Article

1 Cita (Scopus)

Resumen

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.

Idioma originalEnglish
PublicaciónTumor Biology
Volumen41
N.º5
DOI
EstadoPublished - 1 may 2019

Huella dactilar

Epithelial-Mesenchymal Transition
Epigenomics
Non-Small Cell Lung Carcinoma
Lung Neoplasms
Transcription Factors
Neoplasms
Genes
Transforming Growth Factors
Thyroid Neoplasms
Genetic Promoter Regions
Osteogenesis
Cell Movement
Prostatic Neoplasms
Survival Rate
Gene Expression
Cell Line
Mortality
Enzymes
Adenocarcinoma of lung

ASJC Scopus subject areas

  • Cancer Research

Citar esto

Herreño, Angélica María ; Ramírez, Andrea Carolina ; Chaparro, Viviana Paola ; Fernandez, María José ; Cañas, Alejandra ; Morantes, Carlos Fabian ; Moreno, Olga María ; Brugés, Ricardo Elias ; Mejía, Juan Andrés ; Bustos, Fernando José ; Montecino, Martín ; Rojas, Adriana P. / Role of RUNX2 transcription factor in epithelial mesenchymal transition in non-small cell lung cancer lung cancer : Epigenetic control of the RUNX2 P1 promoter. En: Tumor Biology. 2019 ; Vol. 41, N.º 5.
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title = "Role of RUNX2 transcription factor in epithelial mesenchymal transition in non-small cell lung cancer lung cancer: Epigenetic control of the RUNX2 P1 promoter",
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-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.",
keywords = "epigenetic, epithelial mesenchymal transition, histone, lung cancer, RUNX2",
author = "Herre{\~n}o, {Ang{\'e}lica Mar{\'i}a} and Ram{\'i}rez, {Andrea Carolina} and Chaparro, {Viviana Paola} and Fernandez, {Mar{\'i}a Jos{\'e}} and Alejandra Ca{\~n}as and Morantes, {Carlos Fabian} and Moreno, {Olga Mar{\'i}a} and Brug{\'e}s, {Ricardo Elias} and Mej{\'i}a, {Juan Andr{\'e}s} and Bustos, {Fernando Jos{\'e}} and Mart{\'i}n Montecino and Rojas, {Adriana P.}",
year = "2019",
month = "5",
day = "1",
doi = "10.1177/1010428319851014",
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Herreño, AM, Ramírez, AC, Chaparro, VP, Fernandez, MJ, Cañas, A, Morantes, CF, Moreno, OM, Brugés, RE, Mejía, JA, Bustos, FJ, Montecino, M & Rojas, AP 2019, 'Role of RUNX2 transcription factor in epithelial mesenchymal transition in non-small cell lung cancer lung cancer: Epigenetic control of the RUNX2 P1 promoter', Tumor Biology, vol. 41, n.º 5. https://doi.org/10.1177/1010428319851014

Role of RUNX2 transcription factor in epithelial mesenchymal transition in non-small cell lung cancer lung cancer : Epigenetic control of the RUNX2 P1 promoter. / Herreño, Angélica María; Ramírez, Andrea Carolina; Chaparro, Viviana Paola; Fernandez, María José; Cañas, Alejandra; Morantes, Carlos Fabian; Moreno, Olga María; Brugés, Ricardo Elias; Mejía, Juan Andrés; Bustos, Fernando José; Montecino, Martín; Rojas, Adriana P.

En: Tumor Biology, Vol. 41, N.º 5, 01.05.2019.

Resultado de la investigación: Article

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.

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

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U2 - 10.1177/1010428319851014

DO - 10.1177/1010428319851014

M3 - Article

VL - 41

JO - Tumor Biology

JF - Tumor Biology

SN - 1010-4283

IS - 5

ER -