Specific patterns of long non-coding RNA expression in benign and malignant thyroid nodules

Abstract

Abstract Background Although there are increasing evidences of lncRNA role in cancer progression, and of its possible diagnostic and therapeutic significance, lncRNA in thyroid neoplasms are poorly investigated: studies are limited to papillary cancer, the differences in variants of papillary carcinoma are rarely considered, there are no investigations of lncRNA in benign nodules, follicular and anaplastic carcinomas. Methods To evaluate lncRNA expression in follicular adenoma (FA), follicular and classical variants of papillary carcinoma (fvPTC/clPTC), follicular (FTC) and anaplastic (ATC) carcinomas, a comprehensive dataset of 8 independent Microarray experiments on Affymetrix Human Genome U133 Plus 2.0 Array and RNA-Seq experiments (TCGA and PRJEB11591 projects) was analyzed. In silico validation of differential expression was performed. Putative functions of aberrantly expressed lncRNA were determined via co-expression and enrichment analysis of Gene Ontology, KEGG, Reactome terms. Results The analysis revealed 8 lncRNA general for all investigated neoplasms, 22 - general for papillary carcinomas, 32 - specific for clPTC, 1 - for fvPTC, and 177 - specific for ATC. No lncRNA differentially expressed in FTC and FA was found. There are strong clustering of ATC, clustering of clPTC and fvPTC, no clustering within the FTC and FA. LncRNA found to be specific for ATC are probably associated with anaplastic features and cancer progression. Potential functions of lncRNA general for all studied neoplasms - L1CAM interactions; general for papillary carcinomas - tryptophan metabolism; specific for fvPTC - cell polarity and WNT signaling; specific for clPTC - extracellular matrix organization and endoderm formation; specific for ATC - cell cycle and mitosis. Known oncogenic and tumor suppressor lncRNA (NR2F1-AS1, LINC00511, SLC26A4-AS1, CRNDE, LINC01116, RMST) are found in thyroid carcinomas for the first time. Conclusions Common and specific patterns of lncRNA expression in main histological subtypes of thyroid nodules are determined. The findings enhance the understanding of lncRNA in thyroid cancer progression. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.