Knockdown of circ_NEK6 Decreased 131I Resistance of Differentiated Thyroid Carcinoma via Regulating miR-370-3p/MYH9 Axis

Radioresistance is a crucial factor for the failure of iodine 131 (I-131)-based radiotherapy for differentiated thyroid carcinoma (DTC). This study aimed to explore the effect of circ_NEK6 on the development of I-131 resistance in DTC and its potential mechanism. In this study, we demonstrated that circ_NEK6 expression was significantly elevated in I-131-resistant DTC tissues and cell lines. Knockdown of circ_NEK6 significantly repressed I-131 resistance via inhibiting cell proliferation, migration, invasion abilities, and inducing cell apoptosis and DNA damage in I-131-resistant DTC cells. Mechanistically, knockdown of circ_NEK6 suppressed I-131 resistance in DTC by upregulating the inhibitory effect of miR-370-3p on the expression of myosin heavy chain 9 (MYH9). In vivo experiments showed that circ_NEK6 inhibition aggravated I-131 radiation-induced inhibition of xenograft tumor growth. Taken together, knockdown of circ_NEK6 repressed I-131 resistance in DTC cells by regulating the miR-370-3p/MYH9 axis, indicating that circ_NEK6 may act as a potential biomarker and therapeutic target for DTC patients with I-131 resistance.