CircTBCD/IGF2BP2 complex stabilizes IGF-1R mRNA in an m6A-dependent manner to promote bone metastasis in nasopharyngeal carcinoma

Bone metastasis is the leading cause of death in patients with nasopharyngeal carcinoma (NPC), yet the underlying mechanisms of bone metastasis are unclear. Circular RNAs (circRNAs) play key roles in various physiological processes in tumor cells, however, the role of circRNAs in NPC bone metastasis and the underlying mechanisms remain to be elucidated. We constructed nasopharyngeal carcinoma cell lines with a high propensity for bone metastasis and screened for differentially expressed circRNAs by circRNA-Seq. CircTBCD (circbaseID: hsa_circ_0005245) expression was assessed by qRT-PCR. The effect of circTBCD on NPC tumor development was evaluated in vitro and in vivo. The regulatory mechanism of circTBCD in NPC was investigated using FISH, RNA pull-down, RNA immunoprecipitation, RNA stability and gene-specific m6A. CircTBCD expression was upregulated in NPC and was associated with poorer survival. Furthermore, circTBCD was shown to promote proliferation, migration, and bone metastasis in NPC. Mechanistically, circTBCD synergizes with IGF2BP2 to stabilize IGF-1R mRNA through an m6A-dependent pathway and ultimately promoting bone metastasis in NPC. In conclusion, these findings identify an unreported circRNA, circTBCD and demonstrate a novel, circTBCD-based mechanism involved in the regulation of the propensity of NPC to bone metastasis, suggesting that circTBCD potentially acts as a valuable prognostic biomarker and a promising therapeutic target for the treatment of bone-metastatic NPC.