BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
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2026
·Vol. 1872
·期 6
·168257
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IF 5
Yan Guo,Yuanyong Feng,Xiangning Ni,Xuan Zhang,Xiao Fang,Tongtong Li,Ning Wang
Oral squamous cell carcinoma (OSCC) is a common malignant tumor in the head and neck region and clinically characterized by relatively high invasiveness and a propensity for metastasis. Patients generally exhibit nonsatisfactory prognosis. Beyond the classical endothelium-dependent angiogenesis pathway, vasculogenic mimicry (VM), a nonclassical blood supply mechanism whereby tumor cells themselves form microcirculatory conduits, plays a significant role in tumor progression. However, the regulatory mechanism of VM formation remains to be fully understood. U2AF homologous motif kinase 1 (UHMK1) is a regulatory protein possessing serine/threonine kinase activity and RNA-binding capability and was found to be overexpressed in OSCC tissues in our previous research. The present study aimed to explore the association between UHMK1 expression in OSCC and VM formation and elucidate the potential molecular mechanisms by which UHMK1 regulates VM development. Immunohistochemistry (IHC) results demonstrated that UHMK1 upregulation in OSCC was significantly correlated with VM structure, and both were associated with poor clinical outcomes and shortened patient survival time. In vitro experiments revealed that UHMK1 knockdown markedly suppressed VM formation in OSCC cells. Bioinformatics prediction and co-immunoprecipitation (co-IP) assays confirmed the interaction between UHMK1 and stathmin1 (STMN1). Further investigations indicated that UHMK1 stabilized STMN1 protein expression by inhibiting its ubiquitin-proteasome degradation pathway, and these two might jointly activate the PI3K/AKT/mTOR signaling pathway to regulate VM formation. The current study revealed the key role of UHMK1-STMN1 in coregulating VM formation in OSCC, providing new insights into the tumor microenvironment and identifying potential targets for anti-angiogenic therapy.
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ACS Omega
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2026
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IF 5.2
Leina Gao,Dixin Cui,Xu Gao,Xiaoling Luan,Huali Gao
Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy of the head and neck. Current treatment strategies, including surgery, radiotherapy, and chemotherapy, are limited by moderate efficacy and severe side effects, highlighting the need for novel therapeutic approaches. Wogonin (Wo), a natural flavonoid, has shown antiproliferative, pro-apoptotic, and antimetastatic activities in various cancer models; however, its effect on OSCC has not been investigated. In this study, Wo-loaded poly(lactic-co-glycolic acid) nanoparticles (PW NPs) were prepared to enhance water solubility and achieve sustained drug release. In vitro assays, including CCK-8, flow cytometry, live/dead staining, and wound healing assays, revealed that PW NPs significantly inhibited OSCC cell proliferation, induced apoptosis, and reduced cell migration. Network pharmacology analysis and qRT-PCR further suggested that Wo exerts its therapeutic effects through the EGFR signaling pathway. Hemolysis testing and histological examination of major organs confirmed the favorable biocompatibility of the nanoparticles. This study provides the first systematic evidence of the therapeutic potential of Wo in OSCC and lays a foundation for its further preclinical development.
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JOURNAL OF BIOENERGETICS AND BIOMEMBRANES
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2023
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IF 3
Zhang Meixia,Wang Zhonghou,Yang Guang,Han Linfu,Wang Xiaofeng
Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy with increasing mortality and high recurrence. In this work, we aim to explore the functional role of NFE2 like bZIP transcription factor 1 (NFE2L1) in OSCC progression. Based on databases analysis, we found that NFE2L1 was overexpressed in OSCC tumor tissues, and elevated NFE2L1 level induced poor prognosis of OSCC patients. Our results showed that NFE2L1 is upregulated in OSCC cells and overexpression of NFE2L1 promotes cell proliferation, and reduces the sensitivity of OSCC cells to erastin-induced ferroptosis. NFE2L1 upregulation decreased the levels of Fe 2+ , lipid reactive oxygen species and content of malondialdehyde, and increased the level of the key negative regulator of ferroptosis, GPX4 and SLC7A11. In NFE2L1 suppressed cells, these trends were reversed. Further results of dual luciferase reporter and chromatin immunoprecipitation assays confirmed that NFE2L1 could bind to the promoter of Holliday junction recognition protein (HJURP) to increase the transcriptional activity of HJURP, thus upregulating its expression. Inhibition of HJURP attenuated the proliferation and ferroptosis inhibition in NFE2L1 upregulated cells. In vivo tumorigenicity assay further proved that NFE2L1 promotes OSCC tumor growth. In summary, NFE2L1 restrains ferroptosis by transcriptionally regulating HJURP and participates in the progress of OSCC. Thus, NFE2L1 plays a key role in OSCC development and may be a promising therapeutic target for OSCC.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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转录调控
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CHEMICAL ENGINEERING JOURNAL
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2026
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IF 12.5
Jin Li,Bin Zhang,Bingxin Wang,Xiaoxiao Zhang
ZDHHC15 regulates YAP localization and YAP/CYR61 signaling in OSCC. • PA supports OSCC migration through lipid metabolism-linked signaling. • R-LPA@siZDHHC15 enables targeted siRNA delivery and photothermal response. • The nanoplatform suppresses OSCC growth and lung colonization in models. This study aimed to elucidate the molecular mechanism by which ZDHHC15 promotes oral squamous cell carcinoma (OSCC) progression through regulation of the YAP/CYR61 signaling axis. Metabolomic and transcriptomic analyses revealed prominent lipid metabolic reprogramming in OSCC cells, with palmitic acid (PA) driving activation of the YAP transcriptional program and promoting cell migration and lung colonization. Functional experiments showed that ZDHHC15 enhanced YAP nuclear localization and transcriptional activity, leading to increased CYR61 expression and establishment of the ZDHHC15/YAP/CYR61 signaling axis. In addition, we developed a novel nanoplatform, R-LPA@siZDHHC15, which exhibited photothermal responsiveness and tumor-targeted delivery in vivo . When combined with photothermal therapy, this platform suppressed OSCC cell proliferation and tumor growth under the tested conditions. Collectively, these findings provide mechanistic insight into OSCC progression and support targeting the ZDHHC15/YAP/CYR61 axis as a potential therapeutic strategy, while further control and thermal-monitoring studies are needed to fully define the nanotherapeutic contribution. Schematic representation of the molecular mechanism by which R-LPA@siZDHHC15 modulates the YAP/CYR61 axis, thereby achieving combined photothermal and gene therapy to suppress OSCC progression. Download: Download high-res image (152KB) Download: Download full-size image
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Journal of Materials Chemistry B
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2026
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IF 5.7
Lingling Wei,Haoyu Jin,Zhongke Ji,Haoyang Tian,Jiayang Han,Yanyan Liu,Wanjia Li,Di Liu,Hui Song
Oral squamous cell carcinoma (OSCC) remains a challenging malignancy with high recurrence and metastasis rates, often limited by insufficient immunogenicity and a suppressive tumor microenvironment. Immunogenic cell death (ICD) offers a promising approach to convert cell death into antitumor immunity, yet its efficacy depends on precise modulation of autophagy and endoplasmic reticulum stress (ERS). Here, we report that combining the BET inhibitor JQ1 with the autophagy inhibitor chloroquine (CQ) synergistically amplifies ERS, leading to enhanced ICD in OSCC models. This combination promotes robust damage-associated molecular pattern (DAMP) release, dendritic cell activation, and antigen-specific CD8⁺ T-cell responses. To enable localized and efficient delivery, we engineered self-assembled JQ1/CQ nanoparticles stabilized through π–π stacking and integrated them into dissolvable cryomicroneedles. This minimally invasive platform ensures sustained drug release, improves tumor accumulation, and minimizes systemic exposure. Our study not only elucidates a druggable autophagy–ERS–ICD axis but also provides a versatile transdermal delivery strategy with potential applicability to a range of solid tumors.
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Cell Death & Disease
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2026
·Vol. 17
·期 1
·218
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IF 12.2
Zhang Ziyun,Li Yi,Hu Jingjiang,Tang Xingjie,Li Zhanpeng,Sun Xiaoyan,Feng Dade,Yao Yixin,Mao Chao,Tao Yongguang,Xie Li,Luo Huaiqing,Li Yufei,Yu Xing,Peng Xiaoning,Cong Li,Jiang Yiqun
Oral squamous cell carcinoma (OSCC) is an aggressive malignancy characterized by poor prognosis, largely attributable to cancer stem cell (CSC) persistence and ferroptosis resistance. However, the molecular mechanisms that coordinately regulate stemness maintenance and ferroptosis suppression in OSCC remain insufficiently characterized. In this study, KIF20A was identified as significantly overexpressed in OSCC and strongly correlated with adverse clinical outcomes. An integrative approach identified DHX9 as a candidate interactor of KIF20A. Mechanistic investigations revealed that KIF20A regulates DHX9 nucleocytoplasmic distribution and inhibits TRIM21-mediated K48-linked polyubiquitination at DHX9-K755, thereby preventing its proteasomal degradation and enhancing protein stability. Elevated DHX9 enhanced SOX2 mRNA stability, leading to upregulation of SOX2, a central regulator of both CSC maintenance and ferroptosis resistance. Functionally, KIF20A promoted CSC phenotypes, inhibited ferroptosis in vitro and in vivo, and activated the PI3K/AKT signaling pathway. Notably, treatment with ENMD-2076 (identified through Connectivity Map analysis) significantly reduced KIF20A expression, attenuated CSC characteristics, augmented cisplatin sensitivity, and exerted marked antitumor activity. These findings elucidate a novel KIF20A-DHX9-SOX2 regulatory axis that simultaneously governs CSC maintenance and ferroptosis evasion in OSCC. Targeting KIF20A, either as a monotherapy or in combination with chemotherapy, may offer a promising strategy to improve therapeutic outcomes in OSCC.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2025
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IF 6.1
Qixuan He,Anquan Ma,Ziqing Yang,Xinyu Pang,Chen Li,Jiayong Diao,Yuxuan Liu,Quanzhen Liu,Qingyue Zhang,Zuoqing Dong,Dongjiao Zhang
Background Bisphenol A (BPA), an environmental pollutant, has been implicated in oral squamous cell carcinoma (OSCC) progression, yet its molecular mechanisms remain unclear. This study explores the role of GABBR1 in BPA-induced OSCC malignancy. Methods Bioinformatics analysis identified GABBR1 as a key gene in OSCC. Expression patterns and clinical relevance were assessed using TCGA, GTEx, and HPA databases. Molecular docking and dynamics simulations further elucidated the binding interaction between BPA and GABBR1. Functional assays, including western blot, immunofluorescence, CCK-8, EdU, and transwell evaluated the effects of BPA exposure and GABBR1 knockdown on OSCC cell function. Transwell co-culture, RT-PCR and ELISA assays examined exosome-mediated interactions between OSCC cells and macrophages. Results BPA exposure enhanced OSCC proliferation, migration, and invasion while promoting stemness through the GABBR1/MEK/ERK signaling pathway. Additionally, it induced M2 macrophage polarization via exosomal communication, contributing to an immunosuppressive microenvironment. Conclusion This study uncovers a novel mechanism by which BPA promotes OSCC progression via GABBR1-mediated signaling and exosome-driven immunomodulation, highlighting GABBR1 as a potential therapeutic target in BPA-associated OSCC.
研究领域:
肿瘤学
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分子生物学
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免疫学
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环境毒理学
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转化医学
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CELLULAR SIGNALLING
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2023
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IF 4.8
Yunyun Li,Ruizhe Li,Hui Qin,Hongliu He,Shanshan Li
Ovarian tumor domain, ubiquitin aldehyde binding 1 (OTUB1), a deubiquitinating enzyme known to regulate the stability of downstream proteins, has been reported to regulate various cancers tumorigenesis, yet its direct effects on oral squamous cell carcinoma (OSCC) progression are unclear. Bioinformatics analysis was performed to screen for genes of interest, and in vitro and in vivo studies were carried out to investigate the function and mechanism of OTUB1 in OSCC. We found that OTUB1 was abnormally elevated in OSCC tissues and positively associated with the pathological stage and tumor stage. Knockdown of OTUB1 impaired the malignance of OSCC cells - suppressed cell proliferation, invasion, migration, and xenografted tumor growth. OTUB1 silencing also drove tumor-associated macrophage M1 polarization but suppressed M2 polarization, and the induction of M1 polarization inhibited the survival of OSCC cells. However, OTUB1 overexpression exerted the opposite effects. Furthermore, the protein network that interacted with the OTUB1 protein was constructed based on the GeneMANIA website. Receptor for activated C kinase 1 (RACK1), a facilitator of OSCC progression, was identified as a potential target of the OTUB1 protein. We revealed that OTUB1 positively regulated RACK1 expression and inhibited RACK1 ubiquitination. Additionally, RACK1 upregulation reversed the effects of OTUB1 knockdown on OSCC progression. Overall, we demonstrated that OTUB1 might regulate OSCC progression by maintaining the stability of the RACK1 protein. These findings highlight the potential roles of the OTUB1/RACK1 axis as a potential therapeutic target in OSCC.
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Nature Communications
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2025
·Vol. 16
·期 1
·1-19
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IF 15.7
Qi Houbao,Gao Haiting,Li Meihui,Sun Tianyong,Gu Xiufeng,Wei Li,Zhi Mengfan,Li Zixuan,Fu Dachuan,Liu Yiran,Wei Ziyi,Dou Yu,Feng Qiang
Parvimonas micra ( P. micra ), an opportunistic oral pathogen associated with multiple cancers, has limited research on its role in oral squamous cell carcinoma (OSCC). This study shows that P. micra is enriched in OSCC tissues and positively correlated with tumor metastasis and stages. P. micra infection promotes OSCC metastasis by inducing hypoxia/HIF-1α, glycolysis, and autophagy. Mechanistically, P. micra surface protein TmpC binds to CKAP4, a receptor overexpressed in OSCC, facilitating bacterial attachment and invasion. This interaction activates HIF-1α and autophagy via CKAP4-RanBP2 and CKAP4-NBR1 pathways, driving metastasis. Targeting CKAP4 with masitinib or antibodies impairs P. micra attachment and abolishes P. micra -promoted OSCC metastasis in vitro and in vivo. Together, our findings identify P. micra as a pathogen that promotes OSCC metastasis and highlight that TmpC-CKAP4 interaction could be a potential therapeutic target for OSCC.
研究领域:
肿瘤学
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微生物学
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分子生物学
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癌症研究
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International Journal of Nanomedicine
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2025
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IF 6.5
Zheng Zhang,Xiang Sun,Zihan Gao,Xin Lv,Hui Jia,Bin Huang,Chengwan Xia,Xudong Yang
Introduction Oral squamous cell carcinoma (OSCC) has a poor prognosis due to its immunosuppressive tumor microenvironment (TME), in which tumor-associated macrophages (TAMs) play a pivotal role in promoting disease progression and therapeutic resistance. This study examines whether Prussian blue nanoparticles (PB NPs) could reprogram TAMs and block tumor-stroma communication in OSCC.Methods PB NPs were synthesized using polyvinylpyrrolidone-assisted coprecipitation and characterized by transmission electron microscopy, dynamic light scattering, and UV-Vis spectroscopy. In vitro, their effects on macrophage polarization were assessed via immunofluorescence, Western blotting (CD206/CD86), and ELISA (TGF-β1/IL-6/TNF-α). The impact on OSCC-macrophage interaction was evaluated using CCK-8 assays, transwell co-culture systems with conditioned media. In vivo, xenograft-bearing mice were used to assess PB NP effects on OSCC-TAM crosstalk. Tumor growth, Ki67 proliferation index, and TAM phenotypes (CD206+/CD86+) were analyzed. Systemic biocompatibility was further assessed through CCK-8 in vitro and hematological profiling and histopathological examination in vivo.Results PB NPs (diameter 57.43 ± 22.25 nm; zeta potential −17.36mV) were successfully made and showed good biocompatibility in vitro and in vivo. In vitro, they shifted M2 TAMs toward anti-tumor M1 phenotypes, reducing CD206 and TGF-β1 while increasing CD86 and pro-inflammatory cytokines (IL-6, TNF-α). This change disrupted OSCC-TAM communication, limiting tumor growth and migration. In vivo, PB NPs reduced tumor volume, lowered the Ki67+ cell ratio, and increased the intratumoral M1/M2 macrophage ratio.Conclusion Prussian blue nanoparticles effectively modulate the immunosuppressive TME in OSCC by shifting TAM polarization from the pro-tumor M2 phenotype to the anti-tumor M1 phenotype, thereby interrupting critical tumor-stroma interactions. Given their intrinsic immunomodulatory properties and favorable biosafety profile, PB NPs represent a promising and safe therapeutic strategy targeting the TME in OSCC.
研究领域:
纳米医学
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免疫学
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肿瘤学
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生物医学工程
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药理学
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Nanoscience and Nanotechnology Letters
·
2020
·Vol. 12
·期 7
·946-952
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IF 1.128
Mou Fengping,Xiao Li,Xu Yuanqin
This study aims to investigate the therapeutic effect of a paclitaxel-loaded nano-drug (PTX-mPEGPLA) on oral squamous cell carcinoma (OSCC). PTX-mPEG-PLA nanoparticle (NP) was prepared by loading paclitaxel into the mPEG-PLA nanoparticle and purified by a thin-film hydration method.
C57BL/6 mice were used to establish a murine OSCC model. The mice were treated with saline control (G1), paclitaxel (G2), or PTX-mPEG-PLA NPs (G3). After 4 weeks of differential treatment, the saliva of mice in the G1, G2, and G3 groups was collected to detect the concentration of protein
markers of OSCC. Also, venous blood and cancer tissues of mice in the three groups were collected for drug concentration measurements. The paclitaxel concentration and retention in G3 mice were significantly higher and more prolonged than those in G2 mice, respectively (P < 0.05).
Compared to the level of OSCC protein markers in the saliva of mice in G1 and G2 that in G3 was the lowest. PTX-mPEG-PLA NPs demonstrates effective targeting in the treatment of oral squamous cell carcinoma in mice. It can deliver the drug to the cancerous tissues, increase the drug retention
in the same tissues, and effectively inhibit the proliferation and metastasis of malignant tumors.
研究领域:
肿瘤学
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药理学
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纳米技术
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实验医学
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JOURNAL OF CONTROLLED RELEASE
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2024
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IF 10.5
Borui Zhao,Xuan Qin,Rui Fu,Maosen Yang,Xin Hu,Shaorong Zhao,Yange Cui,Qingxiang Guo,Wei Zhou
Chemoresistance to cisplatin remains a significant challenge affecting the prognosis of advanced oral squamous cell carcinoma (OSCC). However, the specific biomarkers and underlying mechanisms responsible for cisplatin resistance remain elusive. Through comprehensive bioinformatic analyses, we identified a potential biomarker, BCL2 associated athanogene-1 (BAG1), showing elevated expression in head and neck squamous cell carcinoma (HNSCC). Since OSCC represents the primary pathological type of HNSCC, we investigated BAG1 expression in human tumor tissues and cisplatin resistant OSCC cell lines, revealing that silencing BAG1 induced apoptosis in cisplatin-resistant cells both in vitro and in vivo . This effect led to impaired cell viability of cisplatin resistant OSCC cells and indicated a positive correlation between BAG1 expression and the G1/S transition during cell proliferation. Based on these insights, the administration of a CDK4/6 inhibitor in combination with cisplatin effectively overcame cisplatin resistance in OSCC through the CDK4/6-BAG1 axis. Additionally, to enable simultaneous drug delivery and enhance synergistic antitumor efficacy, we developed a novel supramolecular nanodrug LEE011-FFERGD/CDDP, which was validated in an OSCC orthotopic mouse model. In summary, our study highlights the potential of a combined administration of CDK4/6 inhibitor and cisplatin as a promising therapeutic regimen for treating advanced or cisplatin resistant OSCC.
研究领域:
肿瘤学
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药理学
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分子生物学
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癌症治疗
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