Long Non-Coding RNAs in the Cell Fate Determination of Neoplastic Thymic Epithelial Cells

Abstract

Thymic Epithelial Tumors (TETs) arise from epithelial cells of the thymus and are very rare neoplasms comprising Thymoma, Thymic carcinoma, and Thymic Neuroendocrine tumors that still require in-depth molecular characterization. Long non-coding RNAs (lncRNAs) are emerging as relevant gene expression modulators involved in the deregulation of several networks in almost all types of human cancer, including TETs. LncRNAs act at different control levels in the regulation of gene expression, from transcription to translation, and modulate several pathways relevant to cell fate determination under normal and pathological conditions. The activity of lncRNAs is strongly dependent on their expression, localization, and post-transcriptional modifications. Starting from our recently published studies, this review focuses on the involvement of lncRNAs in the acquisition of malignant traits by neoplastic thymic epithelial cells, and describes the possible use of these molecules as targets for the design of novel therapeutic approaches specific for TET. Furthermore, the involvement of lncRNAs in myasthenia gravis (MG)-related thymoma, which is still under investigation, is discussed.

Keywords: MALAT1; lncRNA - long noncoding RNA; miRNA - microRNA; myasthenia gravis; ncRNAs (non coding RNAs); thymic carcinoma; thymic epithelial tumors (TETs); thymoma.

Figure 1

Contribution of lncRNAs in TETs and MG. LINC00174 and LOXL1-AS1 are up-regulated in thymoma and thymic carcinoma, where they act as sponges of miR-145-5p and miR-525-5p, respectively, promoting cell growth, metastasis, migration, and lipid metabolism and inhibiting cell death. LncRNAs are deregulated in MG, an autoimmune disease strongly associated with thymoma. Oebiotech_1193 and XLOC_003810 are overexpressed in MG patients and are involved in inflammatory pathways.

Figure 2

Different roles of lncRNA MALAT1 in TETs and MG. MALAT1 has an oncogenic role in TETs. It promotes cell proliferation by acting as a sponge of miR-145-5p. MALAT1 is m⁶A-modified due to METTL3 overexpression in TET and induces c-MYC protein, further contributing to proliferation. In MG, MALAT1 plays a protective role by binding mir-338-3p and avoiding T lymphocyte activation.