Human microRNA expression in sporadic and FAP-associated desmoid tumors and correlation with beta-catenin mutations

// Aldo Cavallini 1, * , Maria Teresa Rotelli 2, * , Catia Lippolis 1 , Domenico Piscitelli 3 , Rosa Digennaro 2 , Claudia Covelli 3 , Nicola Carella 1 , Matteo Accetturo 4 and Donato Francesco Altomare 2 1 Laboratory of Cellular and Molecular Biology, National Institute for Digestive Diseases, IRCCS “Saverio de Bellis”, Castellana Grotte (BA), Italy 2 General Surgery and Liver Transplantation Unit, Department of Emergency and Organ Transplantation (DETO), University of Bari “Aldo Moro”, Bari, Italy 3 Section of Pathology, Department of Emergency and Organ Transplantation (DETO), University of Bari “Aldo Moro”, Bari, Italy 4 Nephrology Unit, Department of Emergency and Organ Transplantation (DETO), University of Bari “Aldo Moro”, Bari, Italy * These authors contributed equally to this work Correspondence to: Aldo Cavallini, email: cavaldo@libero.it Keywords: desmoid tumor, microRNA, CTNNB1 mutations, tetraspanin3 (TSPAN3) mRNA, serpin family A member 3 (SERPINA3) mRNA Received: November 16, 2016      Accepted: February 22, 2017      Published: March 19, 2017 ABSTRACT Desmoid tumors (DT) are rare, benign, fibroblastic neoplasm with challenging histological diagnosis. DTs can occur sporadically or associated with the familial adenomatous polyposis coli (FAP). Most sporadic DTs are associated with β-catenin gene ( CTNNB1 ) mutations, while mutated APC gene causes FAP disease. microRNAs (miRNAs) are involved in many human carcinogenesis. The miRNA profile was analyzed by microarray in formalin-fixed, paraffin-embedded (FFPE) specimens of 12 patients (8 sporadic, 4 FAP-associated) and 4 healthy controls. One hundred and one mRNAs resulted dysregulated, of which 98 in sporadic DTs and 8 in FAP-associated DTs, 5 were shared by both tumors. Twenty-six miRNAs were then validated by RT-qPCR in 23 sporadic and 7 FAP-associated DT samples matched with healthy controls. The qPCR method was also used to evaluate the CTNNB1 mutational status in sporadic DTs. The correlation between sporadic DTs and miRNA expression showed that miR-21-3p increased in mutated versus wild-type DTs, while miR-197-3p was decreased. The mRNA expression of Tetraspanin3 and Serpin family A member 3, as miR-21-3p targets, and L1 Cell Adhesion Molecule, as miR-197-3p target, was also evaluate. CTNNB1 mutations associated to miRNA dysregulation could affect the genesis and the progression of this disease and help histological diagnosis of sporadic DTs.