title: Haplotypes of the HLA-G 3' Untranslated Region Respond to Endogenous Factors of HLA-G+ and HLA-G- Cell Lines Differentially.
abstract: 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.
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives, Institut des Maladies Emergentes et des Thérapies Innovantes, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis, Paris, France.|Université Paris-Diderot, Sorbonne Paris-Cité, UMR_E5, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Poras
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives, Institut des Maladies Emergentes et des Thérapies Innovantes, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis, Paris, France.|Université Paris-Diderot, Sorbonne Paris-Cité, UMR_E5, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France.|Lebanese University, School of Medicine, Hadath, Lebanon.
authors.forename: Layale
authors.initials: L
authors.lastname: Yaghi
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives, Institut des Maladies Emergentes et des Thérapies Innovantes, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis, Paris, France.|Université Paris-Diderot, Sorbonne Paris-Cité, UMR_E5, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France.|Programa de Pós-graduação em Ciências da Saúde, Centro de Ciências da Saúde. Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brasil.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Martelli-Palomino
authors.affiliation: Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Celso T
authors.initials: CT
authors.lastname: Mendes-Junior
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives, Institut des Maladies Emergentes et des Thérapies Innovantes, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis, Paris, France.|Université Paris-Diderot, Sorbonne Paris-Cité, UMR_E5, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France.|Departamento de Biologia Celular, Embriologia e Genética, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianopolis, Santa Catarina, Brasil.
authors.forename: Yara Costa Netto
authors.initials: YC
authors.lastname: Muniz
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives, Institut des Maladies Emergentes et des Thérapies Innovantes, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis, Paris, France.|Université Paris-Diderot, Sorbonne Paris-Cité, UMR_E5, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France.|Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Natalia F
authors.initials: NF
authors.lastname: Cagnin
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives, Institut des Maladies Emergentes et des Thérapies Innovantes, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis, Paris, France.|Université Paris-Diderot, Sorbonne Paris-Cité, UMR_E5, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France.|Departamento de Biologia Celular, Embriologia e Genética, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianopolis, Santa Catarina, Brasil.|Divisão de Imunologia Clínica, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brasil.
authors.forename: Bibiana
authors.initials: B
authors.lastname: Sgorla de Almeida
authors.affiliation: Department of Pathology, School of Medicine, Universidade Estadual Paulista, Unesp, Botucatu, São Paulo, Brazil.
authors.forename: Erick C
authors.initials: EC
authors.lastname: Castelli
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives, Institut des Maladies Emergentes et des Thérapies Innovantes, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis, Paris, France.|Université Paris-Diderot, Sorbonne Paris-Cité, UMR_E5, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France.
authors.forename: Edgardo D
authors.initials: ED
authors.lastname: Carosella
authors.affiliation: Divisão de Imunologia Clínica, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brasil.
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Donadi
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives, Institut des Maladies Emergentes et des Thérapies Innovantes, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis, Paris, France.|Université Paris-Diderot, Sorbonne Paris-Cité, UMR_E5, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D020029:Base Pairing / Q000235:genetics; D001483:Base Sequence; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D059951:HLA-G Antigens / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics; D008156:Luciferases / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D011110:Polymorphism, Genetic
chemical_list: D020413:3' Untranslated Regions; D059951:HLA-G Antigens; D008156:Luciferases