Abstract
Background: Nasopharyngeal carcinoma (NPC) is characterized by pronounced metastatic and invasive properties. Emerging research has elucidated that circular RNAs (circRNAs) are intricately associated with the pathogenesis of NPC, potentially serving as critical mechanisms in tumorigenesis and as promising therapeutic targets for NPC. Methods: The expression levels of circRNAs were analyzed in NPC using reverse transcription quantitative PCR (RT-qPCR). Wound healing, transwell, and clone formation assays were conducted to examine the metastatic potential of NPC. Cell proliferation and apoptosis assays were performed to evaluate cell proliferation and survival. 3D spheroid cultures, RNA pull-down, LC-MS, RNA-sequencing, and luciferase reporter assays were carried out to examine the mechanisms of circPPP1CB in NPC progression. NPC xenograft tumor models were estimated to verify the mechanisms of circPPP1CB in tumor growth and metastasis of NPC in vivo. Results: CircPPP1CB subtype, hsa_circ_0007439, that was more highly expressed in NPC patients with distant metastasis than in those without distant metastasis. Hsa_circ_0007439 overexpression specifically promotes proliferation and inhibits the apoptosis of NPC cells. Further experiments indicated that hsa_circ_0007439 overexpression was correlated with increased tumor growth and distant metastasis of NPC cells. Mechanistically, hsa_circ_0007439 upregulated KRT1 expression by acting as a sponge for miR-1275 and miR-1293. This led to increased proliferation and metastatic progression in NPC by activating the JAK/STATs signaling pathway. Conclusions: This study is the first to demonstrate that hsa_circ_0007439 functions as a competitive endogenous RNA to upregulate KRT1 expression, thereby promoting the metastasis of NPC, suggesting that hsa_circ_0007439 serve as a potential diagnostic biomarker and therapeutic target for NPC.