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.
Highlights
Long non coding RNAs represent a class of non-coding RNAs, usually longer than 200 nucleotides, which play functional role through different mechanisms of action, according to their localization[1]
We show the involvement of LINC00174 and SCD5, one of the five genes belonging to LINC00174-associated signature, in the regulation of migration and lipid metabolism in TC1889 thymic carcinoma cells
As miR-145-5p is a key tumor suppressor in TET33, where it is silenced by epigenetic regulation[32], we here focused on positively correlated Long non coding RNAs (lncRNAs)/ mRNA pairs upregulated in thymic epithelial tumors (TETs) and presenting a binding site for miR-145-5p (Supplementary Table 2)
Summary
Long non coding RNAs (lncRNAs) represent a class of non-coding RNAs, usually longer than 200 nucleotides, which play functional role through different mechanisms of action, according to their localization[1]. Cytoplasmic lncRNAs participate to post transcriptional regulation, mRNA turnover, protein stability and modulation of signaling pathways[5]. One of the well-known roles of lncRNAs is to act as sponges for microRNAs: Official journal of the Cell Death Differentiation Association. Through various mechanisms of action, lncRNAs participate to the regulation of a wide range of biological processes, such as cellular proliferation and differentiation, survival and apoptosis, invasion, migration, and metastasis formation[8]. All these phenotypes, together, contribute to cancer development and progression[9,10,11]. Deregulation of a large number of lncRNAs has been associated to different types of cancer tissues[12], including breast cancer[13], colorectal cancer[14], urologic cancer[15], hepatocellular carcinoma[16], leukemia[17,18], melanoma[19], and possibly others
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