Yang Kaifan, Hu Yanjun, Ma Yuan, Zhu Ziyan, Dai Jiawen, Mao Xinyuan, Liu Shuyi, Cai Longmei, Lin Yanling, Yu Bin
Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, China.; Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.; The First School of Clinical Medicine, Southern Medical University, Guangzhou, China.
The First School of Clinical Medicine, Southern Medical University, Guangzhou, China.
Int J Biol Macromol. 2025 Aug;319(Pt 2):145390. doi: 10.1016/j.ijbiomac.2025.145390. Epub 2025 Jun 19.
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.
骨转移是鼻咽癌（NPC）患者死亡的主要原因，然而，骨转移的潜在机制尚不清楚。环状RNA（circRNAs）在肿瘤细胞的各种生理过程中发挥关键作用，然而，circRNAs在NPC骨转移中的作用及其潜在机制仍有待阐明。我们构建了具有高骨转移倾向的鼻咽癌细胞系，并通过circRNA测序筛选差异表达的circRNAs。通过qRT-PCR评估CircTBCD（circbaseID：hsa_circ_0005245）的表达。在体外和体内评估circTBCD对NPC肿瘤发展的影响。使用FISH、RNA下拉、RNA免疫沉淀、RNA稳定性和基因特异性m6A研究circTBCD在NPC中的调控机制。CircTBCD表达在NPC中上调，并且与较差的生存率相关。此外，circTBCD被证明可促进NPC的增殖、迁移和骨转移。机制上，circTBCD与IGF2BP2协同作用，通过m6A依赖性途径稳定IGF-1R mRNA，最终促进NPC的骨转移。总之，这些发现鉴定了一种未报道的circRNA，circTBCD，并证明了一种基于circTBCD的新机制参与调控NPC向骨转移的倾向，表明circTBCD可能作为一种有价值的预后生物标志物和治疗骨转移性NPC的有前景的治疗靶点。
