Rotelli Maria Teresa, Refolo Maria Grazia, Lippolis Catia, Cavallini Aldo, Picciariello Arcangelo, Piscitelli Domenico, Altomare Donato Francesco
Department of Emergency and Organ Transplantation (DETO), University of Bari "Aldo Moro", Bari, Italy.
Laboratory of Cellular and Molecular Biology, Department of Clinical Pathology, National Institute of Gastroenterology, "Saverio de Bellis" Research Hospital, Castellana Grotte, Bari, Italy.
Oncotarget. 2020 Jun 30;11(26):2484-2492. doi: 10.18632/oncotarget.27622.
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.
信号通路在驱动家族性腺瘤性息肉病（FAP）相关的散发性硬纤维瘤（DT）的失控发展中起关键作用。Wnt/β-连环蛋白信号通路与DT之间的关系已得到广泛研究，但尚未确定能够检测其组织学亚型的可靠生物标志物用于准确诊断。在本研究中，我们使用经定量PCR（qPCR）确认的微阵列研究了散发性DT（20例患者）和FAP相关DT（7例患者）之间miRNA表达的差异。分析显示有19种miRNA表达失调。其中，FAP相关DT中miR-133b的水平显著低于散发性DT。因此，分析了与miR-133b和β-连环蛋白表达相关的两个mRNA，即SIRT1和ELAVL1。qPCR分析显示，FAP相关DT中SIRT1 mRNA水平显著高于散发性DT，而这两种DT类型之间未观察到ELAVL1表达的差异。此外，在FAP相关DT中观察到miR-133b与SIRT1呈负相关，而在散发性DT中未观察到这种相关性。miR-133b-SIRT1-β-连环蛋白轴可能代表FAP相关DT进展的一种新机制。
