Overexpression of novel long intergenic non-coding RNA LINC02454 is associated with a poor prognosis in papillary thyroid cancer

It has been revealed from microarray data analysis that long intergenic non-coding RNA 02454 (LINC02454) is highly expressed in papillary thyroid cancer (PTC). The aim of the present study was to explore the potential role of LINC02454 in the tumorigenesis of PTC. The mRNA expression levels of LINC02454 were assessed using data from The Cancer Genome Atlas (TCGA) and the GSE66783 cohort in thyroid cancer, and were validated using reverse transcription-quantitative PCR in 104 patients with PTC recruited in the present study. The association between the LINC02454 mRNA expression levels and the clinicopathological features of the 104 patients with PTC were also analyzed. Functional enrichment analyses were conducted on the differentially expressed genes in the high and low LINC02454 expression groups that were identified from the TCGA cohort. RNA interference, using short interfering (si)RNA against LINC02454, was used to investigate the role of LINC02454 in the biological functions of PTC cells in vitro. The expression level of LINC02454 was significantly increased in PTC tissues (P=0.0011) and was significantly associated with a larger tumor size, T stage, an advanced TNM stage and an increased lymph node metastasis (P<0.05), which was consistent with that in the TCGA and GSE66783 cohort. High expression levels of LINC02454 were observed in patients with PTC that also had BRAF mutations (P<0.001), and were significantly associated with a poorer disease-free survival in the TCGA cohort (P<0.05). Functional enrichment analysis indicated that LINC02454-related genes were significantly enriched in Gene Ontology terms, such as ‘positive regulation of cell proliferation’, ‘positive regulation of cell division’ and ‘cell adhesion’, and the following Kyoto Encyclopedia of Genes and Genomes pathways: ‘Pathways in cancer’ ‘proteoglycans in cancer’ and ‘ECM-receptor interaction’. In vitro, the knockdown of LINC02454 markedly arrested the cells in the G(0)/G(1) phase of the cell cycle, and also led to an overall increase in apoptosis, as well as to an unexpected decrease in cell proliferation. LINC02454 may thus potentially function as an oncogene, which inhibits the apoptosis and enhances proliferation of PTC cells. Thus, as suggested by the findings of the present study, LINC02454 may be used as a diagnostic and prognostic biomarker for PTC in the future.