Silencing of cystatin SN abrogates cancer progression and stem cell properties in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) accounts for approximately 80% of total thyroid cancers worldwide. Although the prognosis for early-stage PTC is favorable, the 5-year survival rate of patients with late-stage PTC is still very poor. Cystatin SN (cystatin 1, CST1) facilitates the progression of multiple cancers, but its role in regulating PTC pathogenesis is still largely unknown. In this study, we measured the expression levels of CST1 in PTC clinical tissues and cell lines by real-time quantitative PCR and western blot analysis, and we performed gain- and loss-of-function experiments to examine the effects of CST1 on PTC cell growth, invasion, migration, epithelial-mesenchymal transition and stemness. Tumorigenicity was assessed using in vivo tumor-bearing nude mouse models. As expected, upregulated CST1 was observed in PTC tissues (P < 0.05) and cells, compared with their normal counterparts (P < 0.05); furthermore, patients with PTC with higher levels of CST1 exhibited unfavorable prognosis (P < 0.05). In addition, CST1 ablation inhibited PTC cell growth (P < 0.05) in vivo and in vitro. Silencing of CST1 also inhibited cell motility and epithelial-mesenchymal transition in PTC cells (P < 0.05), whereas CST1 overexpression had the opposite effects on the earlier cellular functions. Notably, up-regulation of CST1 promoted cell spheroid formation (P < 0.05) and increased the expression levels of stemness signatures (P < 0.05) in PTC cells. Collectively, these findings suggest that CST1 functions as an oncogene to facilitate cancer development and promote cancer stem cell properties in PTC cells, increasing our understanding of PTC pathogenesis mechanisms and possibly aiding in the development of potential therapeutic strategies.