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|Title:||Differential regulation of miR‐146a/FAS and miR‐21/FASLG axes in autoimmune lymphoproliferative syndrome due to FAS mutation (ALPS‐FAS)|
|Author:||Marega, Lia Furlaneto|
Teocchi, Marcelo Ananias
Vilela, Maria Marluce dos Santos
|Abstract:||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.|
|Appears in Collections:||FCM - Artigos e Outros Documentos|
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