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The Desmoid Tumor Research Foundation

June 2020

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

Author Information

Rotelli MT(1), Refolo MG(2), Lippolis C(1), Cavallini A(3), Picciariello A(1), Piscitelli D(1), Altomare DF(1,4).

(1)Dept of Emergency and Organ Transplantation, Univ of Bari "Aldo Moro", Bari, Italy. (2)Laboratory of Cellular and Molecular Biology, Dept of Clinical Pathology, National Institute of Gastroenterology, "Saverio de Bellis" Research Hospital, Castellana Grotte, Bari, Italy. (3)Surgical Unit, Dept of Emergency and Organ Transplantation, Univ of Bari "Aldo Moro", Bari, Italy. (4)IRCCS Istituto Tumori Giovanni Paolo II, Bari, Italy.

Publication

Oncotarget

Summary

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 beta-catenin expression, the SIRT1 and ELAVL1 were 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-beta-catenin axis may represent a novel mechanism underlying progression of FAP-associated DT.

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