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Haplotypes of the HLA-G 3’ Untranslated Region Respond to Endogenous Factors of HLA-G+ and HLA-G- Cell Lines Differentially

The immune checkpoint HLA-G prevents maternal rejection of the fetus and contributes in cancer invasion and acceptance of allografts. The 5’ and 3’ regulatory regions of the HLA-G gene are polymorphic and balancing selection probably maintains this variability. It is proposed that nucleotide variati...

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Detalles Bibliográficos
Autores principales: Poras, Isabelle, Yaghi, Layale, Martelli-Palomino, Gustavo, Mendes-Junior, Celso T., Muniz, Yara Costa Netto, Cagnin, Natalia F., Sgorla de Almeida, Bibiana, Castelli, Erick C., Carosella, Edgardo D., Donadi, Eduardo A., Moreau, Philippe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5207740/
https://www.ncbi.nlm.nih.gov/pubmed/28045999
http://dx.doi.org/10.1371/journal.pone.0169032
Descripción
Sumario:The immune checkpoint HLA-G prevents maternal rejection of the fetus and contributes in cancer invasion and acceptance of allografts. The 5’ and 3’ regulatory regions of the HLA-G gene are polymorphic and balancing selection probably maintains this variability. It is proposed that nucleotide variations may affect the level of HLA-G expression. To investigate this issue we aimed to analyze how haplotypes of the 3’ untranslated region (3’UTR) with highest worldwide frequencies, namely UTR-1, UTR-2, UTR-3, UTR-4, UTR-5, UTR-18 and UTR-7, impact the expression of a luciferase reporter gene in vitro. Experiments performed with the HLA-G positive cell lines JEG-3 (choricarcinoma) and FON (melanoma), and with the HLA-G negative cell lines M8 (melanoma) and U251MG (glioblastoma) showed that the HLA-G 3’UTR polymorphism influences the response to endogenous cellular factors and may vary according to the cell type. UTR-5 and UTR-7 impact the activity of luciferase the most whereas UTR-2, UTR-3, UTR-4, and UTR-18 have intermediate impact, and UTR-1 has the lowest impact. These results corroborate the previous associations between amounts of plasma sHLA-G levels and 3’UTR haplotypes in healthy individuals and reinforce that 3’UTR typing may be a predictor of the genetic predisposition of an individual to express different levels of HLA-G.