RETRACTED ARTICLE: Circ-NUP214 Promotes Papillary Thyroid Carcinoma Tumorigenesis by Regulating HK2 Expression Through miR-15a-5p.

Abstract

Circular RNA nucleoporin 214 (circ-NUP214) is a novel-identified circRNA, and has been demonstrated to promote cell tumorigenesis in papillary thyroid carcinoma (PTC). However, the detailed roles and molecular mechanism underlying circ-NUP214 in PTC remain unclear. The expression levels of circ-NUP214, microRNA (miR)-15a-5p, and hexokinase 2 (HK2) were detected by quantitative real-time polymerase chain reaction, western blot or immunohistochemical (IHC) assay. Cell proliferation, apoptosis, migration and invasion were analyzed using cell counting kit-8 assay, 5-Ethynyl-2'-Deoxyuridine (EdU), flow cytometry, and transwell assay, respectively. Glucose metabolism was assessed by analyzing glucose consumption, lactate production, and adenosine triphosphate (ATP)/adenosine diphosphate (ADP) ratios. Murine xenograft models were established for in vivo experiments. The interaction between miR-15a-5p and circ-NUP214 or HK2 was analyzed by the dual-luciferase reporter assay. A significant increase of circ-NUP214 expression in PTC tissues and cells was found. Circ-NUP214 knockdown inhibited cell proliferation, migration, invasion and glycolysis but induced apoptosis in PTC in vitro and reduced tumor growth in vivo. MiR-15a-5p was a target of circ-NUP214, and silencing of miR-15a-5p reversed the inhibitory effects of circ-NUP214 knockdown on PTC cell malignant phenotypes and glycolysis. MiR-15a-5p directly targeted HK2, miR-15a-5p-mediated inhibition of cell proliferation, migration, invasion and glycolysis and the promotion of cell apoptosis in PTC were abolished by HK2 overexpression. Besides that, circ-NUP214 indirectly regulated HK2 expression via miR-15a-5p. Circ-NUP214 promoted PTC tumorigenesis by regulating miR-15a-5p/HK2 axis, suggesting a potential therapeutic target for PTC treatment.