Oncotarget

Research Papers:

The role of miRNA-133b and its target gene SIRT1 in FAP-derived desmoid tumor

Maria Teresa Rotelli _, Maria Grazia Refolo, Catia Lippolis, Aldo Cavallini, Arcangelo Picciariello, Domenico Piscitelli and Donato Francesco Altomare

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Oncotarget. 2020; 11:2484-2492. https://doi.org/10.18632/oncotarget.27622

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Abstract

Maria Teresa Rotelli1,*, Maria Grazia Refolo3,*, Catia Lippolis1, Aldo Cavallini4, Arcangelo Picciariello1, Domenico Piscitelli1 and Donato Francesco Altomare1,2

1 Department of Emergency and Organ Transplantation (DETO), University of Bari “Aldo Moro”, Bari, Italy

2 IRCCS Istituto Tumori Giovanni Paolo II, Bari, Italy

3 Laboratory of Cellular and Molecular Biology, Department of Clinical Pathology, National Institute of Gastroenterology, “Saverio de Bellis” Research Hospital, Castellana Grotte, Bari, Italy

4 Surgical Unit, Department of Emergency and Organ Transplantation (DETO), University of Bari “Aldo Moro”, Bari, Italy

* These authors contributed equally to this work

Correspondence to:

Maria Teresa Rotelli,email: mariateresa.rotelli@uniba.it

Keywords: desmoid tumor; miRNA; familial adenomatous polyposis; B-catenin; Wnt pathway

Received: March 18, 2020     Accepted: May 14, 2020     Published: June 30, 2020

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.


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