Deregulation of dicer and mir-155 expression in liposarcoma.

Bruno Vincenzi,Antonio Giordano,Marco Fioramonti,Angelo Paolo Dei Tos,Giuseppe Perrone,Antonio Russo,Michele Iuliani,Alice Zoccoli,Carla Rabitti,Anna Maria Frezza,Daniele Santini,Andrea Onetti Muda,Giuseppe Tonini,Francesco Pantano,Delia De Lisi

doi:10.18632/oncotarget.3201

Bruno Vincenzi, Antonio Giordano + Show 13 more

Open Access

https://doi.org/10.18632/oncotarget.3201

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Abstract

Liposarcoma (LPS) is the most common soft tissue sarcoma. It has been demonstrated that mir-155 was the most overexpressed miRNA in well-differentiated LPS(WDLPS)/dedifferentiated LPS (DDLPS). The aim of this study is to evaluate the involvement of Dicer, Drosha and mir-155 in development of LPS and their possible role in stratification of different histological subtypes. Dicer, Drosha and mir-155 mRNA levels were analyzed in formalin-fixed paraffin-embedded specimens from patients diagnosed with 62 LPS and compared with samples of adipose tissues of healthy donors. The experimental data were obtained using qRT-PCR comparing Dicer, Drosha and mir-155 expression levels in tumor samples versus normal fat. The tumor samples from LPS patients showed a significantly lower Dicer expression versus normal adipose tissue, while Drosha levels did not differ. Concerning mir155 expression levels, our results demonstrated a significant mir-155 up-regulation in all LPS subtypes versus normal adipose tissue except for WDLS. These findings demonstrate for the first time that Dicer is deregulated in LPS and show that mir-155 is differentially expressed in LPS subgroups and it could be a promising tool to improve LPS disease stratification and differential diagnosis.

Highlights

Liposarcoma (LPS) is one of the most frequent sarcoma of adult representing 25% of soft tissue sarcomas
In order to get preliminary information about Dicer expression in LPS, we analyzed the transcriptomic profiles of 21 MLPS/RLPS, 50 dedifferentiated LPS (DDLPS), 24 pleomorphic LPS (PLPS) and 9 normal fat (GSE 21124) searching for Dicer expression level and we found no significant changes in mRNA levels across the different histologies (Figure 1A and Figure 1B)
To investigate if Dicer and Drosha expression was deregulated in LPS, we compared the mRNA levels of these two genes between cancer specimens and normal adipose tissue

Summary

Introduction

Liposarcoma (LPS) is one of the most frequent sarcoma of adult representing 25% of soft tissue sarcomas. According to its clinic pathological and molecular genetic characteristics, it can be divided in four categories: well-differentiated LPS (WDLPS), dedifferentiated LPS (DDLPS), myxoid/round cell LPS (MLPS/RLPS) and pleomorphic LPS (PLPS) [1]. Classification in these subtypes represents the most important determinant of clinical behavior and outcome [2,3,4,5,6]; little is known about the genetic events that led to a specific LPS subtype. The accurate discrimination between different LPS histologic subtypes based on morphology alone is often a challenge even for an experienced soft tissue pathologist

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