International Journal of Oral Science最新文献_第4页

Fully automatic AI segmentation of oral surgery-related tissues based on cone beam computed tomography images 基于锥形束计算机断层扫描图像的口腔手术相关组织全自动人工智能分割

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2024-05-08 DOI: 10.1038/s41368-024-00294-z

Yu Liu, Rui Xie, Lifeng Wang, Hongpeng Liu, Chen Liu, Yimin Zhao, Shizhu Bai, Wenyong Liu

{"title":"Fully automatic AI segmentation of oral surgery-related tissues based on cone beam computed tomography images","authors":"Yu Liu, Rui Xie, Lifeng Wang, Hongpeng Liu, Chen Liu, Yimin Zhao, Shizhu Bai, Wenyong Liu","doi":"10.1038/s41368-024-00294-z","DOIUrl":"https://doi.org/10.1038/s41368-024-00294-z","url":null,"abstract":"Accurate segmentation of oral surgery-related tissues from cone beam computed tomography (CBCT) images can significantly accelerate treatment planning and improve surgical accuracy. In this paper, we propose a fully automated tissue segmentation system for dental implant surgery. Specifically, we propose an image preprocessing method based on data distribution histograms, which can adaptively process CBCT images with different parameters. Based on this, we use the bone segmentation network to obtain the segmentation results of alveolar bone, teeth, and maxillary sinus. We use the tooth and mandibular regions as the ROI regions of tooth segmentation and mandibular nerve tube segmentation to achieve the corresponding tasks. The tooth segmentation results can obtain the order information of the dentition. The corresponding experimental results show that our method can achieve higher segmentation accuracy and efficiency compared to existing methods. Its average Dice scores on the tooth, alveolar bone, maxillary sinus, and mandibular canal segmentation tasks were 96.5%, 95.4%, 93.6%, and 94.8%, respectively. These results demonstrate that it can accelerate the development of digital dentistry.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"162 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140890509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phenformin activates ER stress to promote autophagic cell death via NIBAN1 and DDIT4 in oral squamous cell carcinoma independent of AMPK 苯乙双胍通过 NIBAN1 和 DDIT4 激活 ER 应激，促进口腔鳞状细胞癌细胞自噬性死亡，而与 AMPK 无关

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2024-05-08 DOI: 10.1038/s41368-024-00297-w

Dexuan Zhuang, Shuangshuang Wang, Huiting Deng, Yuxin Shi, Chang Liu, Xue Leng, Qun Zhang, Fuxiang Bai, Bin Zheng, Jing Guo, Xunwei Wu

{"title":"Phenformin activates ER stress to promote autophagic cell death via NIBAN1 and DDIT4 in oral squamous cell carcinoma independent of AMPK","authors":"Dexuan Zhuang, Shuangshuang Wang, Huiting Deng, Yuxin Shi, Chang Liu, Xue Leng, Qun Zhang, Fuxiang Bai, Bin Zheng, Jing Guo, Xunwei Wu","doi":"10.1038/s41368-024-00297-w","DOIUrl":"https://doi.org/10.1038/s41368-024-00297-w","url":null,"abstract":"The efficient clinical treatment of oral squamous cell carcinoma (OSCC) is still a challenge that demands the development of effective new drugs. Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors, however, not much is known about the influence of phenformin on OSCC cells. We found that phenformin suppresses OSCC cell proliferation, and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro. RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4 (DNA damage inducible transcript 4) and NIBAN1 (niban apoptosis regulator 1). We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy. Further, the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4 (activation transcription factor 4), which was induced by phenformin treatment in OSCC cells. Mechanistically, these results revealed that phenformin triggers endoplasmic reticulum (ER) stress to activate PERK (protein kinase R-like ER kinase), which phosphorylates the transitional initial factor eIF2, and the increased phosphorylation of eIF2 leads to the increased translation of ATF4. In summary, we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth. Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"19 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140890516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcriptomic and cellular decoding of scaffolds-induced suture mesenchyme regeneration 支架诱导缝合间充质再生的转录组和细胞解码

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2024-04-23 DOI: 10.1038/s41368-024-00295-y

Jiayi Wu, Feifei Li, Peng Yu, Changhao Yu, Chuyi Han, Yitian Wang, Fanyuan Yu, Ling Ye

{"title":"Transcriptomic and cellular decoding of scaffolds-induced suture mesenchyme regeneration","authors":"Jiayi Wu, Feifei Li, Peng Yu, Changhao Yu, Chuyi Han, Yitian Wang, Fanyuan Yu, Ling Ye","doi":"10.1038/s41368-024-00295-y","DOIUrl":"https://doi.org/10.1038/s41368-024-00295-y","url":null,"abstract":"Precise orchestration of cell fate determination underlies the success of scaffold-based skeletal regeneration. Despite extensive studies on mineralized parenchymal tissue rebuilding, regenerating and maintaining undifferentiated mesenchyme within calvarial bone remain very challenging with limited advances yet. Current knowledge has evidenced the indispensability of rebuilding suture mesenchymal stem cell niches to avoid severe brain or even systematic damage. But to date, the absence of promising therapeutic biomaterials/scaffolds remains. The reason lies in the shortage of fundamental knowledge and methodological evidence to understand the cellular fate regulations of scaffolds. To address these issues, in this study, we systematically investigated the cellular fate determinations and transcriptomic mechanisms by distinct types of commonly used calvarial scaffolds. Our data elucidated the natural processes without scaffold transplantation and demonstrated how different scaffolds altered in vivo cellular responses. A feasible scaffold, polylactic acid electrospinning membrane (PLA), was next identified to precisely control mesenchymal ingrowth and self-renewal to rebuild non-osteogenic suture-like tissue at the defect center, meanwhile supporting proper osteointegration with defect bony edges. Especially, transcriptome analysis and cellular mechanisms underlying the well-orchestrated cell fate determination of PLA were deciphered. This study for the first time cellularly decoded the fate regulations of scaffolds in suture-bony composite defect healing, offering clinicians potential choices for regenerating such complicated injuries.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"102 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140636189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single cell analysis unveils B cell-dominated immune subtypes in HNSCC for enhanced prognostic and therapeutic stratification 单细胞分析揭示了 HNSCC 中以 B 细胞为主的免疫亚型，有助于加强预后和治疗分层

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2024-04-16 DOI: 10.1038/s41368-024-00292-1

Kang Li, Caihua Zhang, Ruoxing Zhou, Maosheng Cheng, Rongsong Ling, Gan Xiong, Jieyi Ma, Yan Zhu, Shuang Chen, Jie Chen, Demeng Chen, Liang Peng

{"title":"Single cell analysis unveils B cell-dominated immune subtypes in HNSCC for enhanced prognostic and therapeutic stratification","authors":"Kang Li, Caihua Zhang, Ruoxing Zhou, Maosheng Cheng, Rongsong Ling, Gan Xiong, Jieyi Ma, Yan Zhu, Shuang Chen, Jie Chen, Demeng Chen, Liang Peng","doi":"10.1038/s41368-024-00292-1","DOIUrl":"https://doi.org/10.1038/s41368-024-00292-1","url":null,"abstract":"Head and neck squamous cell carcinoma (HNSCC) is characterized by high recurrence or distant metastases rate and the prognosis is challenging. There is mounting evidence that tumor-infiltrating B cells (TIL-Bs) have a crucial, synergistic role in tumor control. However, little is known about the role TIL-Bs play in immune microenvironment and the way TIL-Bs affect the outcome of immune checkpoint blockade. Using single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database, the study identified distinct gene expression patterns in TIL-Bs. HNSCC samples were categorized into TIL-Bs inhibition and TIL-Bs activation groups using unsupervised clustering. This classification was further validated with TCGA HNSCC data, correlating with patient prognosis, immune cell infiltration, and response to immunotherapy. We found that the B cells activation group exhibited a better prognosis, higher immune cell infiltration, and distinct immune checkpoint levels, including elevated PD-L1. A prognostic model was also developed and validated, highlighting four genes as potential biomarkers for predicting survival outcomes in HNSCC patients. Overall, this study provides a foundational approach for B cells-based tumor classification in HNSCC, offering insights into targeted treatment and immunotherapy strategies.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"43 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140556671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tetrahedral framework nucleic acids/hyaluronic acid-methacrylic anhydride hybrid hydrogel with antimicrobial and anti-inflammatory properties for infected wound healing 具有抗菌消炎特性的四面体框架核酸/透明质酸-甲基丙烯酸酐杂化水凝胶，用于感染伤口愈合

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2024-04-16 DOI: 10.1038/s41368-024-00290-3

Cai Qi, Qiang Sun, Dexuan Xiao, Mei Zhang, Shaojingya Gao, Bin Guo, Yunfeng Lin

{"title":"Tetrahedral framework nucleic acids/hyaluronic acid-methacrylic anhydride hybrid hydrogel with antimicrobial and anti-inflammatory properties for infected wound healing","authors":"Cai Qi, Qiang Sun, Dexuan Xiao, Mei Zhang, Shaojingya Gao, Bin Guo, Yunfeng Lin","doi":"10.1038/s41368-024-00290-3","DOIUrl":"https://doi.org/10.1038/s41368-024-00290-3","url":null,"abstract":"Bacterial resistance and excessive inflammation are common issues that hinder wound healing. Antimicrobial peptides (AMPs) offer a promising and versatile antibacterial option compared to traditional antibiotics, with additional anti-inflammatory properties. However, the applications of AMPs are limited by their antimicrobial effects and stability against bacterial degradation. TFNAs are regarded as a promising drug delivery platform that could enhance the antibacterial properties and stability of nanodrugs. Therefore, in this study, a composite hydrogel (HAMA/t-GL13K) was prepared via the photocross-linking method, in which tFNAs carry GL13K. The hydrogel was injectable, biocompatible, and could be instantly photocured. It exhibited broad-spectrum antibacterial and anti-inflammatory properties by inhibiting the expression of inflammatory factors and scavenging ROS. Thereby, the hydrogel inhibited bacterial infection, shortened the wound healing time of skin defects in infected skin full-thickness defect wound models and reduced scarring. The constructed HAMA/tFNA-AMPs hydrogels exhibit the potential for clinical use in treating microbial infections and promoting wound healing.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"12 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140556875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tailored apoptotic vesicles promote bone regeneration by releasing the osteoinductive brake 定制的凋亡囊泡通过释放骨诱导制动器促进骨再生

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2024-04-16 DOI: 10.1038/s41368-024-00293-0

Yawen Cheng, Yuan Zhu, Yaoshan Liu, Xuenan Liu, Yanan Ding, Deli Li, Xiao Zhang, Yunsong Liu

{"title":"Tailored apoptotic vesicles promote bone regeneration by releasing the osteoinductive brake","authors":"Yawen Cheng, Yuan Zhu, Yaoshan Liu, Xuenan Liu, Yanan Ding, Deli Li, Xiao Zhang, Yunsong Liu","doi":"10.1038/s41368-024-00293-0","DOIUrl":"https://doi.org/10.1038/s41368-024-00293-0","url":null,"abstract":"Accumulating evidence has demonstrated that apoptotic vesicles (apoVs) derived from mesenchymal stem cells (MSCs; MSC-apoVs) are vital for bone regeneration, and possess superior capabilities compared to MSCs and other extracellular vesicles derived from MSCs (such as exosomes). The osteoinductive effect of MSC-apoVs is attributed to their diverse contents, especially enriched proteins or microRNAs (miRNAs). To optimize their osteoinduction activity, it is necessary to determine the unique cargo profiles of MSC-apoVs. We previously established the protein landscape and identified proteins specific to MSC-apoVs. However, the features and functions of miRNAs enriched in MSC-apoVs are unclear. In this study, we compared MSCs, MSC-apoVs, and MSC-exosomes from two types of MSC. We generated a map of miRNAs specific to MSC-apoVs and identified seven miRNAs specifically enriched in MSC-apoVs compared to MSCs and MSC-exosomes, which we classified as apoV-specific miRNAs. Among these seven specific miRNAs, hsa-miR-4485-3p was the most abundant and stable. Next, we explored its function in apoV-mediated osteoinduction. Unexpectedly, hsa-miR-4485-3p enriched in MSC-apoVs inhibited osteogenesis and promoted adipogenesis by targeting the AKT pathway. Tailored apoVs with downregulated hsa-miR-4485-3p exhibited a greater effect on bone regeneration than control apoVs. Like releasing the brake, we acquired more powerful osteoinductive apoVs. In summary, we identified the miRNA cargos, including miRNAs specific to MSC-apoVs, and generated tailored apoVs with high osteoinduction activity, which is promising in apoV-based therapies for bone regeneration.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"41 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140556704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Expert consensus on pediatric orthodontic therapies of malocclusions in children 儿童牙齿畸形矫治专家共识

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2024-04-16 DOI: 10.1038/s41368-024-00299-8

Chenchen Zhou, Peipei Duan, Hong He, Jinlin Song, Min Hu, Yuehua Liu, Yan Liu, Jie Guo, Fang Jin, Yang Cao, Lingyong Jiang, Qingsong Ye, Min Zhu, Beizhan Jiang, Wenhua Ruan, Xiao Yuan, Huang Li, Rui Zou, Yulou Tian, Li Gao, Rui Shu, Jianwei Chen, Renkai Liu, Shujuan Zou, Xiaobing Li

{"title":"Expert consensus on pediatric orthodontic therapies of malocclusions in children","authors":"Chenchen Zhou, Peipei Duan, Hong He, Jinlin Song, Min Hu, Yuehua Liu, Yan Liu, Jie Guo, Fang Jin, Yang Cao, Lingyong Jiang, Qingsong Ye, Min Zhu, Beizhan Jiang, Wenhua Ruan, Xiao Yuan, Huang Li, Rui Zou, Yulou Tian, Li Gao, Rui Shu, Jianwei Chen, Renkai Liu, Shujuan Zou, Xiaobing Li","doi":"10.1038/s41368-024-00299-8","DOIUrl":"https://doi.org/10.1038/s41368-024-00299-8","url":null,"abstract":"Malocclusion, identified by the World Health Organization (WHO) as one of three major oral diseases, profoundly impacts the dental-maxillofacial functions, facial esthetics, and long-term development of ~260 million children in China. Beyond its physical manifestations, malocclusion also significantly influences the psycho-social well-being of these children. Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition, by mitigating the negative impact of abnormal environmental influences on the growth. Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development, ranging from fetal stages to the early permanent dentition phase. From an economic and societal standpoint, the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated, underlining its profound practical and social importance. This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children, emphasizing critical need for early treatment. It elaborates on corresponding core principles and fundamental approaches in early orthodontics, proposing comprehensive guidance for preventive and interceptive orthodontic treatment, serving as a reference for clinicians engaged in early orthodontic treatment.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"43 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140556885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The evolution of robotics: research and application progress of dental implant robotic systems 机器人技术的发展：牙科植入机器人系统的研究与应用进展

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2024-04-08 DOI: 10.1038/s41368-024-00296-x

Chen Liu, Yuchen Liu, Rui Xie, Zhiwen Li, Shizhu Bai, Yimin Zhao

引用次数: 0

Periodontitis exacerbates pulmonary hypertension by promoting IFNγ+ T cell infiltration in mice 牙周炎通过促进小鼠 IFNγ+ T 细胞浸润加剧肺动脉高压

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2024-03-28 DOI: 10.1038/s41368-024-00291-2

Xiaoqian Meng, Linjuan Du, Shuo Xu, Lujun Zhou, Boyan Chen, Yulin Li, Chumao Chen, Huilin Ye, Jun Zhang, Guocai Tian, Xuebing Bai, Ting Dong, Wenzhen Lin, Mengjun Sun, Kecong Zhou, Yan Liu, Wuchang Zhang, Shengzhong Duan

{"title":"Periodontitis exacerbates pulmonary hypertension by promoting IFNγ+ T cell infiltration in mice","authors":"Xiaoqian Meng, Linjuan Du, Shuo Xu, Lujun Zhou, Boyan Chen, Yulin Li, Chumao Chen, Huilin Ye, Jun Zhang, Guocai Tian, Xuebing Bai, Ting Dong, Wenzhen Lin, Mengjun Sun, Kecong Zhou, Yan Liu, Wuchang Zhang, Shengzhong Duan","doi":"10.1038/s41368-024-00291-2","DOIUrl":"https://doi.org/10.1038/s41368-024-00291-2","url":null,"abstract":"Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease. In the current study, we showed that experimental periodontitis, which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis, exacerbated hypoxia-induced pulmonary hypertension in mice. Mechanistically, periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs, contributing to pulmonary infiltration of interferon gamma positive (IFNγ+) T cells and aggravating the progression of pulmonary hypertension. In addition, we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis, and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies. Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"68 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140310669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FUT8-mediated aberrant N-glycosylation of SEMA7A promotes head and neck squamous cell carcinoma progression FUT8介导的SEMA7A异常N-糖基化促进头颈部鳞状细胞癌的进展

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2024-03-28 DOI: 10.1038/s41368-024-00289-w

Zhonglong Liu, Xiaoyan Meng, Yuxin Zhang, Jingjing Sun, Xiao Tang, Zhiyuan Zhang, Liu Liu, Yue He

{"title":"FUT8-mediated aberrant N-glycosylation of SEMA7A promotes head and neck squamous cell carcinoma progression","authors":"Zhonglong Liu, Xiaoyan Meng, Yuxin Zhang, Jingjing Sun, Xiao Tang, Zhiyuan Zhang, Liu Liu, Yue He","doi":"10.1038/s41368-024-00289-w","DOIUrl":"https://doi.org/10.1038/s41368-024-00289-w","url":null,"abstract":"SEMA7A belongs to the Semaphorin family and is involved in the oncogenesis and tumor progression. Aberrant glycosylation has been intricately linked with immune escape and tumor growth. SEMA7A is a highly glycosylated protein with five glycosylated sites. The underlying mechanisms of SEMA7A glycosylation and its contribution to immunosuppression and tumorigenesis are unclear. Here, we identify overexpression and aberrant N-glycosylation of SEMA7A in head and neck squamous cell carcinoma, and elucidate fucosyltransferase FUT8 catalyzes aberrant core fucosylation in SEMA7A at N-linked oligosaccharides (Asn 105, 157, 258, 330, and 602) via a direct protein‒protein interaction. A glycosylated statue of SEMA7A is necessary for its intra-cellular trafficking from the cytoplasm to the cytomembrane. Cytokine EGF triggers SEMA7A N-glycosylation through increasing the binding affinity of SEMA7A toward FUT8, whereas TGF-β1 promotes abnormal glycosylation of SEMA7A via induction of epithelial–mesenchymal transition. Aberrant N-glycosylation of SEMA7A leads to the differentiation of CD8+ T cells along a trajectory toward an exhausted state, thus shaping an immunosuppressive microenvironment and being resistant immunogenic cell death. Deglycosylation of SEMA7A significantly improves the clinical outcome of EGFR-targeted and anti-PD-L1-based immunotherapy. Finally, we also define RBM4, a splice regulator, as a downstream effector of glycosylated SEMA7A and a pivotal mediator of PD-L1 alternative splicing. These findings suggest that targeting FUT8-SEMA7A axis might be a promising strategy for improving antitumor responses in head and neck squamous cell carcinoma patients.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"47 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140310588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0