Hsa_circ_0002111/miR-557/DUSP14 axis mediates euthyrox-resistance in papillary thyroid cancer

As one of the most commonly used chemotherapeutic drug for papillary thyroid cancer (PTC), euthyrox affects the therapeutic outcome due to the resistance of euthyrox. Hsa_circ_0002111 is highly expressed in euthyrox-resistant PTC patients, and this study intends to explore its role in euthyrox drug resistance. PTC patient samples were used to screen for Circ_0002111 expression. TPC-1 and K1 PTC cell lines and their corresponding euthyrox-resistant cell lines (TPC-1/euthyrox and K1/euthyrox), and a benign human thyroid follicular cell line (Nthy-ori 3-1) were used in in vitro experiments. Circ_0002111 was knocked down in euthyrox-resistant cell lines, and cell viability and colony formation were detected. Caspase-3 activity assay and nucleosomal fragmentation assay were used for the detection of apoptosis. Luciferase reporter assay and biotin-labeled RNA pulldown assay were used to analyze interactions between Circ_0002111 and miR-557, or miR-557 and DUSP14. The upregulation of Circ_0002111 was found in PTC patient samples and associated with euthyrox-resistance in poor prognosis of PTC patients. Experiments in cell lines showed that Circ_0002111 regulates euthyrox-resistance in PTC cells. Mechanistic studies showed that Circ_0002111 promoted DUSP14 expression through miR-557, and euthyrox-resistance in PTC cells depended on the regulation via miR-557/DUSP14 signaling pathways. In conclusion, Hsa_circ_0002111 promotes euthyrox-resistance of PTC cells by adsorption miR-557 upregulation, suggesting Circ_0002111 might be a potential diagnostic marker and therapeutic target for euthyrox-resistant PTC patients.