ALKBH5-induced circRNA NRIP1 promotes glycolysis in thyroid cancer cells by targeting PKM2.

Although circular RNAs are involved in cell proliferation, differentiation, apoptosis, and invasion, the underlying regulatory mechanisms of circular RNAs in thyroid cancer have not been fully elucidated. This article aimed to study the role of circRNA regulated by N6-methyladenosine modification in papillary thyroid cancer (PTC). Quantitative real-time PCR, western blotting, and immunohistochemistry were used to investigate the expressions of circular RNA nuclear receptor-interacting protein 1 (circNRIP1) in PTC tissues and adjacent non-cancerous thyroid tissues. In vitro and in vivo assays were performed to assess the effects of circNRIP1 on PTC glycolysis and growth. The N6-methyladenosine mechanisms of circNRIP1 were evaluated via methylated RNA immunoprecipitation sequencing, luciferase reporter gene, and RNA stability assays. Results showed that CircNRIP1 levels were significantly up-regulated in PTC tissues. Furthermore, elevated circNRIP1 levels in PTC patients were correlated with high tumor lymph node metastasis stage and larger tumor sizes. Functionally, circNRIP1 significantly promoted glycolysis, PTC cell proliferation in vitro, and tumorigenesis in vivo. Mechanistically, circNRIP1 acted as a sponge for miR-541-5p and miR-3064-5p and jointly up-regulated pyruvate kinase M2 (PKM2) expressions. Knockdown of m 6 A demethylase α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5) significantly enhanced circNRIP1 m 6 A modification and up-regulated its expressions. These results show that ALKBH5 knockdown up-regulates circNRIP1, thus promoting glycolysis in PTC cells. Therefore, circNRIP1 can be a prognostic biomarker and therapeutic target for PTC by acting as a sponge for oncogenic miR-541-5p and miR-3064-5p to up-regulate PKM2 expressions.