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.

LINC00174 is a novel prognostic factor in thymic epithelial tumors involved in cell migration and lipid metabolism / Tito, C.; Ganci, F.; Sacconi, A.; Masciarelli, S.; Fontemaggi, G.; Pulito, C.; Gallo, E.; Laquintana, V.; Iaiza, A.; De Angelis, L.; Benedetti, A.; Cacciotti, J.; Miglietta, S.; Bellenghi, M.; Carè, A.; Fatica, A.; Diso, D.; Anile, M.; Petrozza, V.; Facciolo, F.; Alessandrini, G.; Pescarmona, E.; Venuta, F.; Marino, M.; Blandino, G.; Fazi, F.. - In: CELL DEATH & DISEASE. - ISSN 2041-4889. - 11:11(2020), pp. 1-13. [10.1038/s41419-020-03171-9]

LINC00174 is a novel prognostic factor in thymic epithelial tumors involved in cell migration and lipid metabolism

Tito C.;Masciarelli S.;Iaiza A.;De Angelis L.;Benedetti A.;Miglietta S.;Fatica A.;Diso D.;Anile M.;Petrozza V.;Venuta F.;Fazi F.
2020

Abstract

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.
2020
long non-coding RNAs; miR-145-5p; lipid metabolism; cancer cells migration
01 Pubblicazione su rivista::01a Articolo in rivista
LINC00174 is a novel prognostic factor in thymic epithelial tumors involved in cell migration and lipid metabolism / Tito, C.; Ganci, F.; Sacconi, A.; Masciarelli, S.; Fontemaggi, G.; Pulito, C.; Gallo, E.; Laquintana, V.; Iaiza, A.; De Angelis, L.; Benedetti, A.; Cacciotti, J.; Miglietta, S.; Bellenghi, M.; Carè, A.; Fatica, A.; Diso, D.; Anile, M.; Petrozza, V.; Facciolo, F.; Alessandrini, G.; Pescarmona, E.; Venuta, F.; Marino, M.; Blandino, G.; Fazi, F.. - In: CELL DEATH & DISEASE. - ISSN 2041-4889. - 11:11(2020), pp. 1-13. [10.1038/s41419-020-03171-9]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1457118
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