Sialylated Immunoglobulin G Promotes the Malignant Progression of Oral Squamous Cell Carcinoma through VCP-Mediated NDUFB6 Stabilization Regulated Mitochondrial Oxidative Phosphorylation.

Lin Qiu, Anqi Tao, Linlin Zhang, Yiheng Liao, Gang Zhao, Xiaoyan Qiu, Cuiying Li

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Article in Research (Washington, D.C.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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7 authors.

Lin QiuCentral Laboratory, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China.ORCID https://orcid.org/0000-0001-8572-4881

Anqi TaoCentral Laboratory, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China.

Linlin ZhangCentral Laboratory, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China.

Yiheng LiaoCentral Laboratory, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China.

Gang ZhaoDepartment of Orthodontics, Stomatology College of Jiamusi University, Jiamusi, China.

Xiaoyan QiuDepartment of Immunology, School of Basic Medical Sciences, Peking University, NHC Key Laboratory of Medical Immunology, Beijing, China.

Cuiying LiCentral Laboratory, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The absence of distinct biomarkers for oral squamous cell carcinoma (OSCC) hampers clinical diagnosis and treatment. Previous studies have demonstrated that sialylated immunoglobulin G (SIA-IgG) is up-regulated in a variety of epithelial-derived tumors and plays an important biological role. However, the function of SIA-IgG in OSCC progression is yet to be clarified. The expression characteristics and clinical significance of SIA-IgG were investigated using immunohistochemistry, western blot, and bioinformatics analysis. The biological functions of SIA-IgG were evaluated in vitro and in vivo. The underlying mechanisms of SIA-IgG in OSCC were elucidated using immunoprecipitation, mass spectrometry, and proteomic profiling. Furthermore, we explored the inhibitory effects of an exogenously added SIA-IgG-specific monoclonal antibody, RP215, on OSCC. An elevated level of SIA-IgG was observed in OSCC, and this was linked to poor survival among OSCC patients. Meanwhile, the up-regulation of SIA-IgG and valosin-containing protein (VCP) promoted the malignant progression of OSCC by activating the oxidative phosphorylation pathway. Moreover, SIA-IgG showed potential as a marker of OSCC cancer stem cells. Mechanistically, SIA-IgG enhanced the interaction between VCP and NADH:ubiquinone oxidoreductase subunit B6 (NDUFB6), thereby inhibiting the ubiquitin-proteasome-pathway-mediated degradation of NDUFB6 and sustaining the activation of the oxidative phosphorylation pathway. This inhibitory effect was abrogated by the overexpression of VCP. Furthermore, the SIA-IgG-specific antibody RP215 suppressed the malignant progression of OSCC, both in vitro and in vivo.

Identifiers

PMID42273709

DOI10.34133/research.0985

PMCPMC13248703

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