SOX2-induced upregulation of lncRNA LINC01510 promotes papillary thyroid carcinoma progression by modulating miR-335/SHH and activating Hedgehog pathway

Abstract

LncRNA LINC01510 (LINC01510) was a newly identified tumor-related lncRNA whose dysregulation and potential function have been reported in several tumors. However, the expression, clinical significances, and action mechanisms of LINC01510 in papillary thyroid carcinoma (PTC) are still unclear. In this study, we firstly reported that LINC01510 was highly expressed in both PTC tissues and cell lines. Additionally, we used dual-luciferase reporter assay and confirmed that SOX2 could bind directly to the LINC01510 promoter region, activating its transcription. Functional assays with a series of cell experiments indicated that knockdown of LINC01510 suppressed the proliferation, migration and invasion of SW1736 and TPC-1 cells. Moreover, down-regulation of LINC01510 resulted in accelerated apoptosis by promoting the expression of Caspase3/9. In particular, LINC01510 acted as an endogenous sponge by directly binding miR-335, resulting in the suppression of miR-335 expressions. Besides, we confirmed that SHH was a target of miR-335 and miR-335 over-expression distinctly reduced SHH expression in PTC cells. Finally, in the cytoplasm, we provided evidenced that LINC01510 acted as a sponge for miR-335, reducing its ability to promote SHH expression. In addition, the results of Western blot indicated that knockdown of LINC01510 inhibited the expression of SHH and GLI1, suggesting that Hedgehog pathway was suppressed. Taken together, our findings revealed that the newly identified LINC01510/miR-335/SHH axis could be a therapeutic target for PTC.