Transcriptional Regulation of Yin-Yang 1 Expression through the Hypoxia Inducible Factor-1 in Pediatric Acute Lymphoblastic Leukemia
Por:
Antonio-Andres, Gabriela, Martinez-Ruiz, Gustavo U., Morales-Martinez, Mario, Jimenez-Hernandez, Elva, Martinez-Torres, Estefany, Lopez-Perez, Tania V., Estrada-Abreo, Laura A., Patino-Lopez, Genaro, Juarez-Mendez, Sergio, Davila-Borja, Victor M., Huerta-Yepez, Sara
Publicada:
1 feb 2022
Resumen:
Yin-Yang transcription factor 1 (YY1) is involved in tumor progression,
metastasis and has been shown to be elevated in different cancers,
including leukemia. The regulatory mechanism underlying YY1 expression
in leukemia is still not understood. Bioinformatics analysis reveal
three Hypoxia-inducible factor 1-alpha (HIF-1 alpha) putative binding
sites in the YY1 promoter region. The regulation of YY1 by HIF-1 alpha
in leukemia was analyzed. Mutation of the putative YY1 binding sites in
a reporter system containing the HIF-1 alpha promoter region and CHIP
analysis confirmed that these sites are important for YY1 regulation.
Leukemia cell lines showed that both proteins HIF-1 alpha and YY1 are
co-expressed under hypoxia. In addition, the expression of mRNA of YY1
was increased after 3 h of hypoxia conditions and affect several target
genes expression. In contrast, chemical inhibition of HIF-1 alpha
induces downregulation of YY1 and sensitizes cells to chemotherapeutic
drugs. The clinical implications of HIF-1 alpha in the regulation of YY1
were investigated by evaluation of expression of HIF-1 alpha and YY1 in
108 peripheral blood samples and by RT-PCR in 46 bone marrow samples of
patients with pediatric acute lymphoblastic leukemia (ALL). We found
that the expression of HIF-1 alpha positively correlates with YY1
expression in those patients. This is consistent with bioinformatic
analyses of several databases. Our findings demonstrate for the first
time that YY1 can be transcriptionally regulated by HIF-1 alpha, and a
correlation between HIF-1 alpha expression and YY1 was found in ALL
clinical samples. Hence, HIF-1 alpha and YY1 may be possible therapeutic
target and/or biomarkers of ALL.
Filiaciones:
Unidad de Investigación en Enfermedades Oncológicas, Hospital Infantil de México, Federico Gómez, Mexico City, 06720, Mexico
Division de Investigacion, Facultad de Medicina, Universidad Nacional Autonoma de Mexico, Mexico City, 04510, Mexico
Servicio de Hemato-Oncología, Hospital Infantil de Moctezuma, Mexico City, 15530, Mexico
Consejo Nacional de Ciencia y Tecnología (CONACYT), Mexico City, 03940, Mexico
Laboratorio de Investigación en Inmunología y Proteómica, Hospital Infantil de México, Federico Gómez, Mexico City, 06720, Mexico
Laboratorio de Oncología Experimental, Instituto Nacional de Pediatría, S.S.A., Mexico City, 04530, Mexico
Hosp Infantil Mexico Dr Federico Gomez, Unidad Invest Enfermedades Oncol, Federico Gomez, Mexico City 06720, DF, Mexico
Univ Nacl Autonoma Mexico, Fac Med, Div Invest, Mexico City 04510, DF, Mexico
Hosp Infantil Moctezuma, Serv Hematooncol, Mexico City 15530, DF, Mexico
Consejo Nacl Ciencia & Tecnol CONACYT, Mexico City 03940, DF, Mexico
Hosp Infantil Mexico Dr Federico Gomez, Lab Invest Inmunol & Prote, Federico Gomez, Mexico City 06720, DF, Mexico
Inst Nacl Pediat SSA, Lab Oncol Expt, Mexico City 04530, DF, Mexico
Green Published, gold, All Open Access; Gold
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