CircCGNL1 Suppresses Nasopharyngeal Carcinoma Progression by Targeting IGF2BP3 and Inhibiting AKT/mTOR Signaling

Nasopharyngeal carcinoma (NPC) is a malignant tumor with high metastatic potential and poor prognosis due to late diagnosis and frequent metastasis. Circular RNAs (circRNAs) have emerged as essential regulators in tumor growth, yet the functional role of circCGNL1 in NPC remains unexplored. Expression of circCGNL1 and IGF2BP3 was examined in NPC tissues and cell lines using qRT-PCR and western blot. The circular nature, subcellular localization, and stability of circCGNL1 were validated through RNase R digestion, actinomycin D treatment, and FISH assay. Functional roles of circCGNL1 and IGF2BP3 were assessed by CCK-8, EdU, TUNEL, flow cytometry, Transwell, colony formation, and wound-healing assays. Protein-RNA interactions were evaluated using RIP, RNA pull-down, and immunofluorescence co-localization. In vivo tumorigenicity was analyzed using a subcutaneous xenograft model in BALB/c nude mice. circCGNL1 was notably downregulated in NPC tissues and cell lines and exhibited cytoplasmic localization and high stability. In vitro, overexpression of circCGNL1 inhibited NPC cell proliferation, migration, and invasion while increasing apoptosis, and in vivo, it reduced tumor development. IGF2BP3, an oncogenic RNA-binding protein, was upregulated in NPC and promoted tumor progression. Mechanistically, circCGNL1 directly interacted with IGF2BP3 and negatively regulated the AKT/mTOR pathway by reducing phosphorylation of AKT and mTOR. Rescue assays further revealed that circCGNL1 inhibited NPC cell proliferation, migration, and invasion while increasing apoptosis by suppressing the activation of the AKT/mTOR signaling. This study identifies circCGNL1 as a tumor-suppressive circRNA that inhibits NPC progression by binding to IGF2BP3 and suppressing the AKT/mTOR signaling. These findings reveal a novel regulatory mechanism in NPC and highlight circCGNL1 as a promising biomarker and therapeutic target.