TY - JOUR
T1 - LINC00174 is a novel prognostic factor in thymic epithelial tumors involved in cell migration and lipid metabolism
AU - Masciarelli, Silvia
AU - Tito, Claudia
AU - Ganci, Federica
AU - Sacconi, Andrea
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
PY - 2020
Y1 - 2020
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.
KW - differentiation
KW - non coding RNA
KW - differentiation
KW - non coding RNA
UR - http://hdl.handle.net/10807/166008
U2 - 10.1038/s41419-020-03171-9
DO - 10.1038/s41419-020-03171-9
M3 - Article
VL - 11
SP - 959-N/A
JO - Cell Death and Disease
JF - Cell Death and Disease
SN - 2041-4889
ER -