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https://www.arca.fiocruz.br/handle/icict/18161
EPIGENETIC INACTIVATION OF THE P53-INDUCED LONG NONCODING RNA TP53 TARGET 1 IN HUMAN CANCER
Autor(es)
Diaz-Lagares, Angel
Crujeiras, Ana B
Lopez-Serra, Paula
Soler, Marta
Setien, Fernando
Goyal, Ashish
Sandoval, Juan
Hashimoto, Yutaka
Cardús, Anna Martinez
Gomez, Antonio
Heyn, Holger
Moutinho, Catia
Espada, Jesús
Vidal, August
Paúles, Maria
Galán, Maica
Sala, Núria
Akiyama, Yoshimitsu
Martínez-Iniesta, María
Vallve, Maria de Lourdes Farre
Villanueva, Alberto
Gross, Matthias
Diederichs, Sven
Guil, Sonia
Esteller, Manel
Crujeiras, Ana B
Lopez-Serra, Paula
Soler, Marta
Setien, Fernando
Goyal, Ashish
Sandoval, Juan
Hashimoto, Yutaka
Cardús, Anna Martinez
Gomez, Antonio
Heyn, Holger
Moutinho, Catia
Espada, Jesús
Vidal, August
Paúles, Maria
Galán, Maica
Sala, Núria
Akiyama, Yoshimitsu
Martínez-Iniesta, María
Vallve, Maria de Lourdes Farre
Villanueva, Alberto
Gross, Matthias
Diederichs, Sven
Guil, Sonia
Esteller, Manel
Afiliação
Bellvitge Biomedical Research Institute (IDIBELL). L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program (PEBC). Barcelona, Catalonia, Spain
Bellvitge Biomedical Research Institute (IDIBELL). L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program (PEBC). Barcelona, Catalonia, Spain / Instituto Salud Carlos III. Centro de Investigación Biomédica en Red (CIBER) Fisiopatología de la Obesidad y Nutrición (CIBERobn). Madrid, Spain / Complejo Hospitalario Universitario de Santiago. Endocrine Division. Santiago de Compostela, Spain
Bellvitge Biomedical Research Institute (IDIBELL). L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program (PEBC). Barcelona, Catalonia, Spain. Múltipla - ver em Notas
Bellvitge Biomedical Research Institute (IDIBELL). L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program (PEBC). Barcelona, Catalonia, Spain / Instituto Salud Carlos III. Centro de Investigación Biomédica en Red (CIBER) Fisiopatología de la Obesidad y Nutrición (CIBERobn). Madrid, Spain / Complejo Hospitalario Universitario de Santiago. Endocrine Division. Santiago de Compostela, Spain
Bellvitge Biomedical Research Institute (IDIBELL). L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program (PEBC). Barcelona, Catalonia, Spain. Múltipla - ver em Notas
Resumo em Inglês
Long noncoding RNAs (lncRNAs) are important regulators of cellular homeostasis. However, their contribution to the cancer phenotype still needs to be established. Herein, we have identified a p53-induced lncRNA, TP53TG1, that undergoes cancer-specific promoter hypermethylation-associated silencing. In vitro and in vivo assays identify a tumor-suppressor activity for TP53TG1 and a role in the p53 response to DNA damage. Importantly, we show that TP53TG1 binds to the multifaceted DNA/RNA binding protein YBX1 to prevent its nuclear localization and thus the YBX1-mediated activation of oncogenes. TP53TG1 epigenetic inactivation in cancer cells releases the transcriptional repression of YBX1-targeted growth-promoting genes and creates a chemoresistant tumor. TP53TG1 hypermethylation in primary tumors is shown to be associated with poor outcome. The epigenetic loss of TP53TG1 therefore represents an altered event in an lncRNA that is linked to classical tumoral pathways, such as p53 signaling, but is also connected to regulatory networks of the cancer cell.
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