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IGF2BP3 promotes progression of head and neck cancers through the circHECTD2/hsa_miR_4310/7157-5p/Smad2 signaling axis in an m6A modification–dependent manner

ABSTRACT: Accumulating evidence indicates that N6-methyladenosine (m6A) modification of circular RNAs (circRNAs) plays a pivotal role in regulating cancer progression. However, in head and neck squamous cell carcinoma (HNSCC), the biological functions and underlying mechanisms of m6A modification in circRNAs remain insufficiently elucidated. In this study, we demonstrated that IGF2BP3, an upstream m6A reader, is associated with poor clinical outcomes. IGF2BP3 stabilizes circHECTD2 through binding, and m6A modification enhances this interaction. Mechanistic investigations revealed that IGF2BP3 binds to and stabilizes circHECTD2, which functions as a sponge for hsa-miR-4310 and hsa-miR-7157-5p, thereby preventing the degradation of SMAD2 mRNA and promoting tumor proliferation, invasion, and metastasis in HNSCC. Collectively, these findings suggest that IGF2BP3 and circHECTD2 may serve as promising prognostic biomarkers and therapeutic targets for HNSCC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE313611 | GEO | 2026/04/15

REPOSITORIES: GEO

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Project description:Background: Circular RNAs (circRNAs) represent a newly identified class of non-coding RNAs that can be secreted into body fluids via exosomes and subsequently detected. While the function of circPRMT5 has been partially elucidated in certain tumor types, its role and underlying mechanisms in head and neck squamous cell carcinoma (HNSCC) remain inadequately understood. Furthermore, the diagnostic potential of circPRMT5 in saliva necessitates additional investigation.Methods: The expression of circPRMT5 was quantified using qRT-PCR. The biological function of circPRMT5 in HNSCC progression was confirmed both in vitro and in vivo. RNA sequencing (RNA-Seq) was used to find downstream targets for circPRMT5-IGF2BP3. IGF2BP3 and SERPINE1 expression levels were assessed using qRT-PCR, Western blotting, and immunohistochemistry. Additionally, the localization and interaction of circPRMT5, IGF2BP3 protein, and SERPINE1 in HNSCC were evaluated using RNA-FISH, immunofluorescence (IF), and RNA immunoprecipitation (RIP) assays. Ultimately, saliva exosomes were collected, identified and assessed using Western Blot, electron microscopy, particle size analysis and qRT-PCR.Results: Findings revealed that circPRMT5 was upregulated in HNSCC and promoted its proliferation and metastasis in vitro and in vivo. Mechanistically, circPRMT5 stabilized IGF2BP3 protein, which in turn stabilized SERPINE1 mRNA. Notably, the proliferative, invasive, and migratory effects of circPRMT5 in HNSCC were contingent upon the involvement of IGF2BP3 and SERPINE1. Furthermore, circPRMT5 levels were significantly elevated in the saliva of HNSCC patients, and positively correlated with increased lymph node metastasis and advanced T stage. These findings underscored the high diagnostic and predictive potential of circPRMT5 in HNSCC.Conclusions: CircPRMT5 plays a crucial role in promoting HNSCC proliferation and metastasis via the IGF2BP3-SERPINE1 pathway. It serves as a noninvasive diagnostic biomarker, indicating its potential as a valuable diagnostic and therapeutic target for HNSCC patients.

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IGF2BP3 promotes progression of head and neck cancers through the circHECTD2/hsa_miR_4310/7157-5p/Smad2 signaling axis in an m6A modification–dependent manner

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