Differential regulation of miR-146a/FAS and miR-21/FASLG axes in autoimmune lymphoproliferative syndrome due to FAS mutation (ALPS-FAS).

Marega, Lia Furlaneto; Teocchi, Marcelo Ananias; Dos Santos Vilela, Maria Marluce

Marega, Lia Furlaneto; Teocchi, Marcelo Ananias; Dos Santos Vilela, Maria Marluce.

Afiliação

Marega LF; Laboratory of Pediatric Immunology, Center for Investigation in Pediatrics, Faculty of Medical Sciences, University of Campinas - UNICAMP, Campinas, SP, Brazil.
Teocchi MA; Laboratory of Pediatric Immunology, Center for Investigation in Pediatrics, Faculty of Medical Sciences, University of Campinas - UNICAMP, Campinas, SP, Brazil.
Dos Santos Vilela MM; Laboratory of Pediatric Immunology, Center for Investigation in Pediatrics, Faculty of Medical Sciences, University of Campinas - UNICAMP, Campinas, SP, Brazil.

Clin Exp Immunol ; 185(2): 148-53, 2016 Aug.

Article em En | MEDLINE | ID: mdl-27060458

RESUMO

Most cases of autoimmune lymphoproliferative syndrome (ALPS) have an inherited genetic defect involving apoptosis-related genes of the FAS pathway. MicroRNAs (miRNAs) are a class of small non-coding regulatory RNAs playing a role in the control of gene expression. This is the first report on miRNAs in ALPS patients. We studied a mother and son carrying the same FAS cell surface death receptor (FAS) mutation, but with only the son manifesting the signs and symptoms of ALPS-FAS. The aim was to analyse, by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the peripheral blood mononuclear cells (PBMC) relative expression of miR-146a and miR-21, including their passenger strands and respective targets (FAS and FASLG). In comparison with healthy matched control individuals, miR-21-3p was over-expressed significantly (P = 0·0313) in the son, with no significant change in the expression of miR-146a, miR-146a-3p and miR-21. In contrast, the mother had a slight under-expression of the miR-146a pair and miR-21-3p (P = 0·0625). Regarding the miRNA targets, FAS was up-regulated markedly for the mother (P = 0·0078), but down-regulated for the son (P = 0·0625), while FASLG did not have any significant alteration. Taken together, our finding clearly suggests a role of the miR-146a/FAS axis in ALPS-FAS variable expressivity in which FAS haploinsufficiency seems to be compensated only in the mother who had the miR-146a pair down-regulated. As only the son had the major clinical manifestations of ALPS-FAS, miR-21-3p should be investigated as playing a critical role in ALPS physiopathology, including the development of lymphoma.

Assuntos

Síndrome Linfoproliferativa Autoimune/genética; Proteína Ligante Fas/genética; MicroRNAs/genética; Mutação; Receptor fas/genética; Adulto; Apoptose; Síndrome Linfoproliferativa Autoimune/fisiopatologia; Regulação para Baixo; Feminino; Regulação da Expressão Gênica; Humanos; Leucócitos Mononucleares; Masculino; Pessoa de Meia-Idade; Reação em Cadeia da Polimerase em Tempo Real; Regulação para Cima

Palavras-chave

apoptosis; gene expression regulation; immunologic deficiency syndromes

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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptor fas / MicroRNAs / Proteína Ligante Fas / Síndrome Linfoproliferativa Autoimune / Mutação Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Exp Immunol Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido

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