Haplotypes of the HLA-G 3′ untranslated region respond to endogenous factors of HLA-G+ and HLA-G- cell lines differentially

Poras, Isabelle; Yaghi, Layale; Martelli-Palomino, Gustavo; Mendes, Celso T.; Muniz, Yara Costa Netto; Cagnin, Natalia F.; De Almeida, Bibiana Sgorla; Castelli, Erick C. [UNESP]; Carosella, Edgardo D.; Donadi, Eduardo A.; Moreau, Philippe

Haplotypes of the HLA-G 3′ untranslated region respond to endogenous factors of HLA-G+ and HLA-G- cell lines differentially

Arquivos

2-s2.0-85008192046.pdf (2.21 MB)

Data

2017-01-01

Autores

Poras, Isabelle

Yaghi, Layale

Martelli-Palomino, Gustavo

Mendes, Celso T.

Muniz, Yara Costa Netto

Cagnin, Natalia F.

De Almeida, Bibiana Sgorla

Castelli, Erick C.

Carosella, Edgardo D.

Donadi, Eduardo A.

Tipo

Artigo

Direito de acesso

Acesso aberto

Resumo

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.