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 participate 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. The aberrant expression of lncRNAs is associated to different diseases, including cancer. Thymoma and Thymic Carcinoma are the most frequent subtypes of Thymic Epithelial Tumors (TETs) that arise from thymic epithelial cells. The aim of this study is to characterize lncRNAs contribution in TETs. Starting from a gene expression analysis on tumor (T) tissues vs normal (N) counterparts, we identified deregulation of several positively correlated lncRNAs/mRNAs that shared binding sites for miR-145-5p, a tumor suppressor microRNA downregulated in TETs. We validated the inverse correlation between lncRNAs/mRNAs pairs and miR-145-5p expression in thymic carcinoma cell line TC1889 and in primary cell cultures from normal and neoplastic thymic tissues. Silencing of specific lncRNAs led to decrease of cell proliferation, migration and an alteration of lipid metabolism. Coherently, among miR-145-5p putative target genes, we identified genes involved in lipid metabolism pathway, as those that catalyze the formation of monounsaturated fatty acids (MFA). To explore whether alteration of lipid metabolism affects cell migration, we silenced specific members of lipid metabolism pathway and observed a decrease of cell motility. Taken together, our findings suggest that the identified lncRNAs and their regulated pathways play a relevant role in migration and lipid metabolism control in TETs.