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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Marega, Lia Furlaneto ; Teocchi, Marcelo Ananias ; dos Santos Vilela, Maria Marluce
Total Authors: 3
Document type: Journal article
Source: CLINICAL AND EXPERIMENTAL IMMUNOLOGY; v. 185, n. 2, p. 148-153, AUG 2016.
Web of Science Citations: 3

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=00313) 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=00625). Regarding the miRNA targets, FAS was up-regulated markedly for the mother (P=00078), but down-regulated for the son (P=00625), 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. (AU)

FAPESP's process: 12/06194-9 - Functional, molecular and histopathological approach of autoimmunity and lymphoproliferative syndrome as a manifestation of primary immunodeficiency
Grantee:Maria Marluce dos Santos Vilela
Support Opportunities: Regular Research Grants