TY - JOUR
T1 - LINC00174 is a novel prognostic factor in thymic epithelial tumors involved in cell migration and lipid metabolism
AU - Tito, Claudia
AU - Ganci, Federica
AU - Sacconi, Andrea
AU - Masciarelli, Silvia
AU - Fontemaggi, Giulia
AU - Pulito, Claudio
AU - Gallo, Enzo
AU - Laquintana, Valentina
AU - Iaiza, Alessia
AU - De Angelis, Luciana
AU - Benedetti, Anna
AU - Cacciotti, Jessica
AU - Miglietta, Selenia
AU - Bellenghi, Maria
AU - Carè, Alessandra
AU - Fatica, Alessandro
AU - Diso, Daniele
AU - Anile, Marco
AU - Petrozza, Vincenzo
AU - Facciolo, Francesco
AU - Alessandrini, Gabriele
AU - Pescarmona, Edoardo
AU - Venuta, Federico
AU - Marino, Mirella
AU - Blandino, Giovanni
AU - Fazi, Francesco
N1 - Funding Information:
The research leading to these results received funding from: AIRC IG 2018—ID. 21406 project, Istituto Pasteur Italia—Fondazione Cenci Bolognetti, ‘Progetti Ateneo’ Sapienza University of Rome and PRIN 2017—Prot. 2017TATYMP_003 to F.F.; AIRC IG 2015—ID. 17352 project to A.F. The authors want to thank the Biobank of IRCCS Regina Elena National Cancer Institute (BBIRE), Rome, Italy, for sample and data preservation. The biobank was fully supported by the Scientific Direction of IRCCS Regina Elena National Cancer Institute. We gratefully acknowledge Fabrizio Padula and Ezio Battaglione for technical assistance.
Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - Long non-coding RNAs are emerging as new molecular players involved in many biological processes, such as proliferation, apoptosis, cell cycle, migration, and differentiation. Their aberrant expression has been reported in variety of diseases. The aim of this study is the identification and functional characterization of clinically relevant lncRNAs responsible for the inhibition of miR-145-5p, a key tumor suppressor in thymic epithelial tumors (TETs). Starting from gene expression analysis by microarray in a cohort of fresh frozen thymic tumors and normal tissues, we identified LINC00174 as upregulated in TET. Interestingly, LINC00174 expression is positively correlated with a 5-genes signature in TETs. Survival analyses, performed on the TCGA dataset, showed that LINC00174 and its associated 5-genes signature are prognostic in TETs. Specifically, we show that LINC00174 favors the expression of SYBU, FEM1B, and SCD5 genes by sponging miR-145-5p, a well-known tumor suppressor microRNA downregulated in a variety of tumors, included TETs. Functionally, LINC00174 impacts on cell migration and lipid metabolism. Specifically, SCD5, one of the LINC00174-associated genes, is implicated in the control of lipid metabolism and promotes thymic cancer cells migration. Our study highlights that LINC00174 and its associated gene signature are relevant prognostic indicators in TETs. Of note, we here show that a key controller of lipid metabolism, SCD5, augments the migration ability of TET cells, creating a link between lipids and motility, and highlighting these pathways as relevant targets for the development of novel therapeutic approaches for TET.
AB - Long non-coding RNAs are emerging as new molecular players involved in many biological processes, such as proliferation, apoptosis, cell cycle, migration, and differentiation. Their aberrant expression has been reported in variety of diseases. The aim of this study is the identification and functional characterization of clinically relevant lncRNAs responsible for the inhibition of miR-145-5p, a key tumor suppressor in thymic epithelial tumors (TETs). Starting from gene expression analysis by microarray in a cohort of fresh frozen thymic tumors and normal tissues, we identified LINC00174 as upregulated in TET. Interestingly, LINC00174 expression is positively correlated with a 5-genes signature in TETs. Survival analyses, performed on the TCGA dataset, showed that LINC00174 and its associated 5-genes signature are prognostic in TETs. Specifically, we show that LINC00174 favors the expression of SYBU, FEM1B, and SCD5 genes by sponging miR-145-5p, a well-known tumor suppressor microRNA downregulated in a variety of tumors, included TETs. Functionally, LINC00174 impacts on cell migration and lipid metabolism. Specifically, SCD5, one of the LINC00174-associated genes, is implicated in the control of lipid metabolism and promotes thymic cancer cells migration. Our study highlights that LINC00174 and its associated gene signature are relevant prognostic indicators in TETs. Of note, we here show that a key controller of lipid metabolism, SCD5, augments the migration ability of TET cells, creating a link between lipids and motility, and highlighting these pathways as relevant targets for the development of novel therapeutic approaches for TET.
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U2 - 10.1038/s41419-020-03171-9
DO - 10.1038/s41419-020-03171-9
M3 - Article
C2 - 33161413
AN - SCOPUS:85095603160
VL - 11
JO - Cell Death and Disease
JF - Cell Death and Disease
SN - 2041-4889
IS - 11
M1 - 959
ER -