Journal of Oral Pathology & Medicine最新文献

{"title":"Regulation of Exosomal miR-320d/FAM49B Axis by Guanylate Binding Protein 5 Promotes Cell Growth and Tumor Progression in Oral Squamous Cell Carcinoma.","authors":"Kai-Fang Hu, Chih-Wen Shu, Chun-Feng Chen, Cheng-Hsin Lee, Hsiang-Chien Kung, Yu-Hsiang Chou, Chun-Lin Chen, Pei-Feng Liu","doi":"10.1111/jop.13624","DOIUrl":"https://doi.org/10.1111/jop.13624","url":null,"abstract":"<p><strong>Background: </strong>Guanylate binding protein 5 (GBP5) and exosomal miRNAs are involved in tumor progression. While several studies reveal the connection between GBP5 and exosomes for immune response and infection, this relationship in cancer, particularly in oral squamous cell carcinoma (OSCC), remains unexplored.</p><p><strong>Methods: </strong>The exosomal miRNA extracted from the cells was analyzed using next-generation sequencing. Bioinformatic tools were used to predict exosomal miRNA target genes. OSCC cell growth was verified by colony formation, cell viability, and cell cycle analysis. The Cancer Genome Atlas database was used to inspect the prognosis of OSCC patients.</p><p><strong>Results: </strong>Our results showed that OSCC cells treated with exosomes from GBP5-silenced OSCC cells reduced colony formation. Also, 56 differentially expressed exosomal miRNAs were found in GBP5-silenced OSCC cells compared to scrambled OSCC cells. Among them, exosomal miR-320d exhibited the highest negative correlation with GBP5 in OSCC patients. High GBP5/low miR-320d co-expression was linked to reduced disease-free survival (DFS) in patients with OSCC. Interestingly, the inhibitory effect of GBP5-silenced exosomes on OSCC cell growth was reversed by miR-320d inhibitors. Moreover, five miR-320d target genes were predicted, and only Family with Sequence Similarity 49, Member B (FAM49B) showed a negative correlation with miR-320d. A decreased level of FAM49B was found in OSCC cells treated with exosomes derived from GBP5-silenced OSCC cells, while the decreased level of FAM49B was reversed by miR-320d inhibitors. Silencing FAM49B and GBP5-silenced exosomes enhanced the cytotoxicity of paclitaxel. FAM49B was abundantly expressed in tumor tissues, and high FAM49B/low miR-320d and high GBP5/high FAM49B co-expression were linked to reduced DFS of OSCC patients.</p><p><strong>Conclusion: </strong>Our study suggests that GBP5 downregulated exosomal miR-320d may trigger FAM49B expression and facilitate OSCC tumor growth and progression.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2 Entry Factors ACE2, TMPRSS2 and FURIN in Salivary Glands From Primary Sjögren's Disease.","authors":"Fernanda Aragão Felix, Flávia Martins Vasconcelos Filiú, Tarcília Aparecida da Silva, Débora Cerqueira Calderaro, Leandro Augusto Tanure, Maurício Augusto Aquino de Castro, Ricardo Santiago Gomez, Marina Gonçalves Diniz, Sílvia Ferreira de Sousa","doi":"10.1111/jop.13621","DOIUrl":"https://doi.org/10.1111/jop.13621","url":null,"abstract":"<p><strong>Background: </strong>Salivary glands are the reservoir for severe acute respiratory syndrome Coronavirus 2 virus (SARS-CoV-2). It is known that SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2) and FURIN to infect cells. Salivary glands express these entry factors, and it is unclear if these molecules are expressed in salivary glands from primary Sjögren's disease (pSjD). This study assessed ACE2, TMPRSS2, and FURIN gene expression by RT-qPCR in pSjD compared to normal salivary gland and pleomorphic adenoma.</p><p><strong>Methods: </strong>An integrated study of ACE2, TMPRSS2, and FURIN gene expression across pSjD, pleomorphic adenoma, and normal salivary gland by RT-pPCR was performed. The association between gene expression and clinicopathological data was also examined.</p><p><strong>Results: </strong>pSjD showed ACE2 upregulation compared with normal salivary gland and pleomorphic adenoma (p < 0.05). TMPRSS2 and FURIN mRNA levels are also higher in pSjD compared to pleomorphic adenoma (p < 0.05). ACE2 expression levels were associated with anti-SSA/SSB positivity (p < 0.05). A strong correlation was observed between TMPRSS2 and FURIN in pSjD (r = 0.768; p = 0.001).</p><p><strong>Conclusion: </strong>Our analysis revealed a high expression of ACE2 in pSjD. ACE2, TMPRSS2, and FURIN mRNA levels are increased in pSjD in comparison to pleomorphic adenomas. Neither ACE2, TMPRSS2, nor furin was consistently associated with SARS-CoV-2 positivity in pSjD. These findings may guide future investigations on the effects of SARS-CoV-2 in a subset of salivary gland diseases.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AMPK in Chemoradiotherapy-Induced Oral Mucositis.","authors":"Junjie Jiang, Hao Xu, Mingyue Liu, Jiwei Guo, Jing Li, Jianwen Li, Hengtai Bi, Yousen Wang, Zhiliang Wang","doi":"10.1111/jop.13626","DOIUrl":"https://doi.org/10.1111/jop.13626","url":null,"abstract":"<p><strong>Background: </strong>Oral mucositis (OM) is a prevalent adverse effect of radiotherapy and chemotherapy, significantly impacting cancer patients' well-being and potentially increasing mortality rates. Understanding OM's pathogenesis and identifying effective preventative and therapeutic agents are clinically crucial.</p><p><strong>Methods: </strong>This study analyzed RNA-Seq data from the GEO database, focusing on OM samples post-radiotherapy and chemotherapy. Differential gene expression analysis between OM and non-OM groups, followed by gene ontology (GO) enrichment analysis of differentially expressed genes (DEGs), was conducted. LASSO regression identified five potential biomarkers, and CIBERSORT assessed immune infiltration in OM samples. Correlations between biomarkers and immune infiltration were explored, and the connectivity map (CMAP) screened potential therapeutic drugs. The top 10 drugs were validated through molecular docking.</p><p><strong>Results: </strong>A total of 47 DEGs were identified, primarily involved in mitotic sister chromatid separation according to GO enrichment analysis. CIBERSORT analysis revealed significant changes in B cell naive and dendriform cells (DCs) resting content in the OM group. PRKAA2, encoding the AMP-activated protein kinase (AMPK) catalytic subunit, showed a negative correlation with DC resting content. Molecular docking from CMAP identified aloisine and teniposide as potential agents for OM induced by radiotherapy and chemotherapy.</p><p><strong>Conclusion: </strong>AMPK emerges as a crucial regulator in OM post radiotherapy and chemotherapy, implicating sister chromatid separation, where DCs may play a pivotal role. Aloisine and Teniposide appear promising for OM prevention or treatment associated with these treatments.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triptolide Treatment for Oral Squamous Cell Carcinoma by Regulating the LncRNA-MSTRG.24214.1/MiRNA-939-5p/LCN2 Axis.","authors":"Siyan Chen, Zhengmiao Li, Menglin Hu, Yang Yu, Bing Liu, Wuliji Saiyin, Jichen Li","doi":"10.1111/jop.13625","DOIUrl":"https://doi.org/10.1111/jop.13625","url":null,"abstract":"<p><strong>Background: </strong>Although triptolide has demonstrated efficacy in treating oral squamous cell carcinoma (OSCC), its precise molecular mechanism remains unclear. This study investigated the mechanism underlying triptolide's action in lncRNA-mediated competing endogenous RNA (ceRNA) regulation.</p><p><strong>Methods: </strong>The impact of triptolide on OSCC in vivo was validated using a xenograft tumor model. Whole-transcriptome sequencing and bioinformatics analysis were conducted to construct the lncRNA-miRNA-mRNA regulatory network. Relative gene and protein expression levels were confirmed using qRT-PCR and Western blot. Dual-luciferase assays were performed to assess target interactions, while cell proliferation was measured using CCK8 assays, and cell migration and invasion were evaluated via wound healing and transwell assays.</p><p><strong>Results: </strong>Triptolide markedly reduced proliferation, migration, and invasion in Cal27 and Tca8113 cells. After 22 days of triptolide treatment, the tumor volume of mice gradually shrank. This led to significant upregulation of cleaved Caspase-3 and Bax, alongside downregulation of Bcl-2. Transcriptome sequencing and bioinformatics analysis identified 266 differentially expressed mRNAs, 528 lncRNAs, and 85 miRNAs. Enhanced expression of lncRNA MSTRG.24214.1 and mRNA LCN2, along with reduced expression of miR-939-5p, was observed in the triptolide group.</p><p><strong>Conclusions: </strong>The lncRNA-miRNA-mRNA ceRNA network associated with triptolide's impact on OSCC was successfully established. Triptolide suppressed OSCC development and progression both in vitro and in vivo, potentially through modulation of the MSTRG.24214.1-miR-939-5p-LCN2 axis. These findings offer a solid foundation for future personalized triptolide-based therapeutic approaches.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Royal Jelly as a Therapeutic Intervention in Medication-Related Osteonecrosis of the Jaw (MRONJ): An Animal Model Study","authors":"Cihan Topan,&nbsp;Suheyb Bilge,&nbsp;Ahmet Emin Demirbas,&nbsp;Gürkan Ağyüz,&nbsp;Ayça Kara","doi":"10.1111/jop.13627","DOIUrl":"10.1111/jop.13627","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>To evaluate the efficacy of royal jelly in managing experimentally created MRONJ model in rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sixty rats were randomly allocated into control, bisphosphonate (BP), royal jelly (RJ), Treatment, and Preventive groups. A defect was created in the alveolar socket following tooth extraction in the mandible as a surgical procedure in all groups. Before surgery, RJ was administered orally to the RJ group. Zoledronic acid was administered intraperitoneally to induce osteonecrosis in BP, treatment, and preventive group rats. Treatment group rats received RJ orally post-surgery, while preventive group rats received it pre-surgery. Histological and radiographic evaluations were performed post-study completion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Micro-CT examinations demonstrated significantly improved values in RJ-received groups (RJ, treatment, and preventive) compared to BP and control groups (<i>p</i> &lt; 0.001). Immunohistochemical analysis revealed higher mean IL-1β and TNF-α levels in the BP group. The highest IL-1β difference was between BP and preventive groups (<i>p</i> &lt; 0.001). TNF-α expression levels in all RJ-received groups were comparatively close to those of the control group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>RJ enhances soft and hard tissue healing in MRONJ rat models, suggesting its potential as a therapeutic or preventive agent in osteonecrosis management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"54 4","pages":"232-240"},"PeriodicalIF":2.7,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Oral-Systemic Link: Controversies and Policy Implications","authors":"Nicola Cirillo","doi":"10.1111/jop.13619","DOIUrl":"10.1111/jop.13619","url":null,"abstract":"<div>\u0000 \u0000 <p>Oral health has never been more central to the political agenda than it is today, particularly in the context of broader health policy. However, there are important caveats to consider when assessing the oral-systemic nexus.</p>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"54 4","pages":"197-198"},"PeriodicalIF":2.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Need to Improve the Medical Subject Headings (MeSH) and the Excerpta Medica Tree (EMTREE) Thesauri to Perform Systematic Review on Oral Potentially Malignant Disorders","authors":"Vito Carlo Alberto Caponio,&nbsp;Gennaro Musella,&nbsp;Mario Pérez-Sayáns,&nbsp;Lorenzo Lo Muzio,&nbsp;Rui Amaral Mendes,&nbsp;Rosa María López-Pintor","doi":"10.1111/jop.13616","DOIUrl":"10.1111/jop.13616","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Despite recent advancements in the understanding and classification of oral potentially malignant disorders (OPMD), their terminology remains inconsistent and heterogeneous throughout the scientific literature, thus affecting evidence-based decision-making relevant for clinical management of these disorders. Updating this classification represents a necessity to improve the indexing and retrieval of OPMD publications, in particular for systematic reviews and meta-analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Through a critical appraisal of the Medical Subject Headings (MeSH) and Excerpta Medica Tree (EMTREE) thesauri, we assessed gaps in the indexing for OPMD literature and propose improvements for enhanced categorisation and retrieval.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The present study identifies inconsistencies and limitations in the classification of these disorders across the major medical databases, which may be summarized in the following findings: a) The MeSH database lacks a dedicated subject heading for “oral potentially malignant disorders”; b) EMTREE indexing is incomplete, with only 5 out of 11 recognised OPMD having corresponding terms; c) Incoherent controlled vocabulary mappings hinder systematic literature retrieval.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>To ensure accurate evidence synthesis, the authors recommend searching both PubMed and Embase for OPMD studies. Moreover, the use of Embase’s PubMed query translator and Large Language Models, such as ChatGPT, may lead to retrieval biases due to indexing discrepancies, posing challenges for early-career researchers and students. We recommend introducing “oral potentially malignant disorders” as a standardised subject heading. Evidence-based medicine underpins clinical decision support systems, which rely on standardised clinical coding for reliable health information. Enhanced medical ontologies will facilitate structured clinical coding, ensuring interoperability and improving clinical decision support systems.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"54 4","pages":"241-247"},"PeriodicalIF":2.7,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jop.13616","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is Dysplasia the Sole Determinant of the Prognosis in Oral Potentially Malignant Disorders?","authors":"Pelin Güneri,&nbsp;Betul İlhan,&nbsp;Gaye Bolukbasi,&nbsp;Ali Veral,&nbsp;Joel B. Epstein","doi":"10.1111/jop.13617","DOIUrl":"10.1111/jop.13617","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The dynamic nature of oral epithelial dysplasia, involving both progression and regression over time, complicates prognostic predictions for the lesion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This paper addresses the intricacies of this challenge and advocates for a nuanced strategy. It proposes a comprehensive assessment, tailored to individual patients, incorporating genetic, behavioral, and medical factors to enhance the precision of lesion evaluation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"54 4","pages":"248-250"},"PeriodicalIF":2.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jop.13617","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electronic Cigarettes Versus Combustible Cigarettes in Oral Squamous Cell Cancer Patients: A Systematic Review","authors":"Martín Pérez-Leal,&nbsp;Bouchra El Helou,&nbsp;Inés Roger","doi":"10.1111/jop.13618","DOIUrl":"10.1111/jop.13618","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Oral squamous cell carcinoma (OSCC) is associated with tobacco. In order to reduce the burden of smoking, e-cigarettes emerge as devices to aid cessation of tobacco addiction. However, growing evidence shows that e-cigarettes can lead to harmful effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objetives</h3>\u0000 \u0000 <p>The aim is to analyze the prevalence of combustible or electronic cigarette smoking in patients with a diagnosis of OSCC, analyze the prevalence of precancerous lesions in smokers of combustible or electronic cigarettes, and describe the location and differentiation of OSCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>PRISMA guidelines were followed. PubMed, Web of Science, and Scopus were used, introducing specific algorithms related to electronic and combustible cigarettes associated with OSCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 400 potentially eligible articles, 15 met the inclusion criteria: 13 studies on combustible and 2 on e-cigarettes. Regarding combustible, the mean smoking prevalence in patients was 56.38% with a prevalence of precancerous lesions of 2.50%, among other parameters. For the e-cigarette group, the mean prevalence was 4.26% with a prevalence of precancerous lesions of 2.20%. Tongue and lower lip are common and frequent locations in both cigarettes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Despite certain limitations, developing OSCC is mostly associated with combustible cigarettes and to a lesser extent with e-cigarettes. Both cigarettes show a similar prevalence of precancerous lesions, with the tongue as a common and frequent location.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"54 4","pages":"199-206"},"PeriodicalIF":2.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Antisense Transcript-Mediated Regulation of HOXA10-AS in Oral Squamous Cell Carcinoma","authors":"Kanaka Sai Ram Padam,&nbsp;Satyajit Dey Pereira,&nbsp;Naveena A. N. Kumar,&nbsp;Raghu Radhakrishnan","doi":"10.1111/jop.13613","DOIUrl":"10.1111/jop.13613","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The oncogenic role of <i>HOXA10</i>-<i>AS</i> and <i>HOXA10</i> in cancer has been well documented. However, the epigenetic role of <i>HOXA10</i> and the natural antisense-mediated regulation of <i>HOXA10-AS</i> in oral squamous cell carcinoma progression is not understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 35 oral squamous cell carcinoma specimens and 35 adjacent normal clinical specimens were collected and categorized on the basis of their lymph node status. <i>HOXA10-AS</i> and <i>HOXA10</i> expression were analyzed using RT-qPCR. Methyl-capture sequencing was performed using lymph node-negative (<i>n</i> = 6) and lymph node-positive (<i>n</i> = 5) matched cases. The promoter activity of <i>HOXA10</i> was determined using a luciferase assay. ChIP-qPCR was performed to determine histone mark localization in the distal promoter region of <i>HOXA10</i>. A protein–protein interaction network of genome-wide antisense targets was constructed using StringDB, and functional enrichment was performed using the R package ClusterProfiler. Transient siRNA-mediated transfection was performed to target specific exons of the <i>HOXA10-AS</i> gene, followed by subsequent cell proliferation, cell cycle, and cell migration assays and validation of cancer signaling pathways through western blotting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>\u0000 <i>HOXA10-AS</i> and its antisense target <i>HOXA10</i> were significantly overexpressed in the lymph node-positive samples. The transcriptionally active distal promoter of <i>HOXA10</i> consists of a constitutively unmethylated CpG island region (CUR). H3K4me3, H3K27ac, and H3K27me3 histone mark deposition at the adjacent methylated loci of the distal promoter suggest the nature of euchromatin-driven regulation. Genome-wide mapping revealed 11 potential targets of <i>HOXA10</i>-<i>AS</i>. Targeted specific knockdown of <i>HOXA10</i>-<i>AS</i> exons significantly reduced the expression of <i>HOXA10</i> and deregulated its downstream targets, contributing to decreased cell cycle progression and epithelial-to-mesenchymal transition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>\u0000 <i>HOXA10</i>-<i>AS</i> regulates the expression of <i>HOXA10</i> through a natural antisense-mediated mechanism and is epigenetically regulated by constitutively unmethylated marks in the distally enhancing promoter of <i>HOXA10</i>.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"54 4","pages":"217-231"},"PeriodicalIF":2.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jop.13613","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}