The TGF-β-regulated X-inactive specific transcript inhibits papillary thyroid cancer migration and invasion

Abstract

Background: As a common endocrine gland malignancy worldwide, papillary thyroid cancer (PTC) shows a relatively high survival of PTC patients, but their prognosis becomes worse as soon as the lymph nodes are invaded. In our study, we found that a long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) was associated with lymph node metastasis in PTC. Our purpose was to explore the functions and underlying mechanisms of this lncRNA in PTC. Methods: Bioinformatics analyses were performed with data from The Cancer Genome Atlas (TCGA) database. We confirmed the results in PTC tissues using quantitative real time polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH), and then studied the functions using Transwell® invasion and migration assays in vitro with TPC-1 and BCPAP cells. The correlation between XIST and the TGF-β pathway was confirmed using qRT-PCR and western blotting of PTC cell samples. All data were analyzed with SPSS software. Results: Using bioinformatics analyses and RNA detection techniques, we found that lncRNA XIST was associated with lymph node metastasis in PTC. The in vitro assays showed that XIST inhibited PTC cell invasion and migration. Furthermore, we found that XIST expression was correlated with Smad4, a core protein in the TGF-β pathway. Through co-transfection assays in PTC cells, we showed that XIST expression was inhibited by TGF-β, and this promoted PTC cell invasion and migration. Conclusions: We found that lncRNA XIST functioned as an inhibitor of PTC metastasis. Furthermore, TGF-β suppressed the expression of this lncRNA in PTC cells. As XIST is regulated by TGF-β and functions as an inhibitor of PTC metastasis, it may serve as a new biomarker of PTC patient metastasis and prognosis.