Long non-coding RNAs contribution to cell migration and lipid metabolism in thymic epithelial tumor cells

Long non-coding RNAs (lncRNAs) are defined as non-coding transcripts larger than 200 nucleotides that partecipate to gene expression, epigenetic and post-transcriptional regulation. They are emerging as new molecular players involved in many biological processes, such as proliferation, apoptosis, cell cycle, migration and differentiation.1 Therefore, the aberrant expression of lncRNAs was associated to different diseases, including cancer.2 Thymoma and thymic carcinoma are the most frequent subtypes of Thymic epithelial tumors (TETs) that arise from thymic epithelial cells.3 The aim of this study is the characterization of lncRNA LINC00174’s role in TETs. Starting from our gene expression analysis, we identified LINC00174 and positively correlated genes that shared a binding site for miR-145-5p, a tumor suppressor microRNA downregulated in TETs. Here, we confirmed the upregulation of linc00174 and correlated genes in thymic tumor tissue compared to normal thymic tissue, using microarrays analysis. Then, we validated the inverse correlation between LINC00174/mRNAs pairs and miR-145-5p expression on thymic carcinoma TC1889 cell line and on primary cell cultures from normal and neoplastic thymic tissue. To explore functional role of LINC00174 in TETs, we performed a silencing of LINC00174 and as result, we observed a decrease of cellular proliferation, migration and an alteration of lipid metabolism. Interestingly, among the genes positively correlated to LINC00174 and predicted to be targeted by miR-145-5p, we found SCD5, a gene that catalyzes the formation of monounsatured fatty acids from satured fatty acids. On the basis of these data and in order to verify the link between lipid metabolism and cellular migration, we demonstrated that silencing of SCD5 impairs cell motility. Taken together, our findings indicate that LINC00174 and its signature play an important role in migration and lipid metabolism in TETs.