Abstract
Signaling pathways have a key role in driving the uncontrolled development of familial adenomatous polyposis (FAP)- associated and sporadic desmoid tumors (DTs).The relationship between the Wnt/b-catenin signaling pathway and DTs has been extensively studied, but no reliable biomarkers able to detect their histological subtype have been identified for the accurate diagnosis.In this study we studied the differences in miRNA expression between sporadic (20 patients) and FAP-associated DTs (7 patients) using microarray confirmed by quantitative PCR (qPCR). The analysis showed 19 dysregulated miRNAs. Among them miR-133b levels were significantly lower in FAP-associated DT than in sporadic DT. Therefore, two mRNAs, associated to miR-133b and β-catenin expression, the SIRT1 and ELAVL1were analyzed.The qPCR analysis showed that SIRT1 mRNA levels were significantly up-regulated in FAP-associated DT than in sporadic DT, whereas no differences in ELAVL1 expression was observed between these two DT types. In addition, a negative correlation was observed between miR-133b and SIRT1 in FAP-associated DTs, but not in sporadic DTs.The miR-133b-SIRT1-β-catenin axis may represent a novel mechanism underlying progression of FAP-associated DT.
Highlights
Desmoid tumor (DT) is a rare, mesenchymal benign tumor, characterized by monoclonal, fibroblastic proliferation [1] with local invasiveness, high risk of recurrence and even mortality, despite metastatization never occurs
In this study we studied the differences in miRNA expression between sporadic (20 patients) and familial adenomatous polyposis (FAP)-associated DTs (7 patients) using microarray confirmed by quantitative PCR
Nineteen of 2,080 miRNAs identified by the microarray analysis resulted differently expressed in FAPassociated DT compared to sporadic DT
Summary
Desmoid tumor (DT) is a rare, mesenchymal benign tumor, characterized by monoclonal, fibroblastic proliferation [1] with local invasiveness, high risk of recurrence and even mortality, despite metastatization never occurs. Due to the high risk of recurrence, and the possible onset of multifocal DTs, traditional surgical approach has recently been replaced by other conservative medical treatments including antioestrogen therapy, radiotherapy and chemotherapy, as a first option [3,4,5,6]. Most of the desmoid tumors (85-90%) occur sporadically, have a benign prognosis and about 85% of them show a mutation in CTNNB1 gene encoding β-catenin protein. The stability of mutated β-catenin results in the intranuclear accumulation of this protein which subsequently stimulates Wnt pathway
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