Journal of Oral Pathology & Medicine最新文献

{"title":"Assessment of Organ-Specific Fibrotic Biomarkers in Patients With Oral Submucous Fibrosis.","authors":"Nikita Baheti, Gargi Sarode, Abhirami Premarajan, Sachin Sarode","doi":"10.1111/jop.70116","DOIUrl":"10.1111/jop.70116","url":null,"abstract":"<p><strong>Background: </strong>Oral submucous fibrosis is a potentially malignant disorder with a high malignant transformation rate. Areca nut, being the chief etiologic factor, when chewed, is known to be swallowed and absorbed into circulation resulting in several systemic effects. This is the first kind of report presenting serum organ-specific fibrosis biomarkers suggestive of functional and fibrotic changes in the visceral organs.</p><p><strong>Methods: </strong>Various fibrotic biomarkers such as kidney injury molecule-1 (KIM-1), alanine aminotransferace (ALT), aspartate aminotransferase (AST), and its ratio to platelet index (APRI), suppression of tumorigenicity-2 (ST2), Krebs von den Lungen-6 (KL-6) and von Willebrand factor (vWF) were analyzed.</p><p><strong>Results: </strong>The present study evaluated potential systemic fibrotic involvement, modest elevations in ST2 and KL-6 levels in advanced OSF compared to early cases; however, all values remained within normal physiological limits. No significant differences were found between the OSF and healthy groups across all biomarkers. There was no renal involvement, no significant association between liver fibrosis and its systemic biomarkers, and there was minimal vascular involvement. Collectively, these findings support the hypothesis that OSF may be a localized fibrotic disorder with no detectable systemic biomarker alterations in its early to moderate stages.</p><p><strong>Conclusions: </strong>This study provides an important step in bridging localized oral pathology and systemic disease monitoring. No significant systemic fibrosis was observed but methodology, findings, and recommendations offer a strong basis for future research. Despite the presence of evidence that favors a localized disease model for OSF in its early and advanced stages, systemic monitoring in future clinical paradigms is acknowledged.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":"601-604"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906254","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":"Comment on \"COVID-19 Dry Mouth Induced by SARS-CoV-2 Not Binding Directly to ACE2 but Interacting Electrostatically With Lipid Raft in Salivary Glands\".","authors":"Hironori Tsuchiya","doi":"10.1111/jop.70121","DOIUrl":"10.1111/jop.70121","url":null,"abstract":"","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":"509-510"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003236","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":"High Expression of CHD1L, a Potent Oncogene Is Associated With Aggressive Head and Neck Cancer and Poor Survival Outcome.","authors":"Aishvarya Rukmani Panayappan, Chandra Pandi, Vijayashree Priyadharshini Jayaseelan, Paramasivam Arumugam","doi":"10.1111/jop.70114","DOIUrl":"10.1111/jop.70114","url":null,"abstract":"<p><strong>Objective: </strong>Head and Neck Squamous Cell Carcinoma (HNSCC) is one of the most common cancers worldwide and has a significant impact on the lives of patients. This study aimed to examine the role and significance of Chromodomain Helicase/ATPase DNA Binding protein 1-Like (CHD1L) in HNSCC.</p><p><strong>Methods: </strong>CHD1L expression was analyzed using the Cancer Genome Atlas (TCGA-HNSCC) dataset, along with the clinical and clinicopathological features of HNSCC. Additionally, CHD1L mRNA expression was quantified using real-time quantitative PCR (RT-qPCR). The survival rate of patients with HNSCC was assessed using Kaplan-Meier analysis. Furthermore, in silico tools were employed to investigate CHD1L protein networks and functional pathways involved in HNSCC development.</p><p><strong>Results: </strong>mRNA and protein expression studies, along with in vitro and in silico analyses, confirmed that CHD1L expression was significantly higher in HNSCC tissues than in normal tissues. Clinicopathological analysis revealed associations between CHD1L expression and HPV status, nodal metastasis, disease stage, and tumor grade. Elevated CHD1L levels are also associated with poor patient survival. Functional enrichment analysis showed that CHD1L was associated with HNSCC progression.</p><p><strong>Conclusion: </strong>CHD1L is significantly upregulated in HNSCC and associated with poor survival outcomes. This suggests that CHD1L may serve as a potential therapeutic target and prognostic marker for HNSCC. Further research is necessary to explore the functional role of CHD1L in the development and progression of HNSCC.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":"546-554"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911992","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":"Molecular Insights Into Epithelial Detachment in Odontogenic Keratocyst: The Role of Matrix Metalloproteinases and Effects of Marsupialization.","authors":"Arthur Henrique Soares Pacheco, Marina Rocha Fonseca Souza, Alline Teixeira Valeriano, Savio Almeida Botrel, Laís Santos Câmara, Amanda Gabrielle De Sousa, Carolina Cavalieri Gomes, Vanessa de Fátima Bernardes, Ricardo Santiago Gomez, Marina Gonçalves Diniz","doi":"10.1111/jop.70112","DOIUrl":"10.1111/jop.70112","url":null,"abstract":"<p><strong>Introduction: </strong>Odontogenic keratocyst (OKC) is a developmental odontogenic cyst characterized by a fragile epithelial lining attachment to the capsula and high recurrence rates. Matrix metalloproteinases (MMPs) and adhesion-related proteins (TLN1, FBLN1) may contribute to epithelial detachment, which could facilitate lesion recurrence. This study investigated the mRNA expression of MMP2, MMP9, TLN1, and FBLN1 in OKCs and their association with epithelial detachment, including the impact of marsupialization.</p><p><strong>Methods: </strong>Gene expression was analyzed by RT-qPCR in samples from OKCs (n = 10), marsupialized OKCs (n = 5), and oral mucosa controls (n = 4). Gelatinase activity was assessed by gelatin zymography in fresh samples (OKCs n = 7; oral mucosa n = 4). Histological sections were digitally measured to quantify areas of epithelial detachment. Correlation analyses were performed between mRNA expression levels and epithelial separation.</p><p><strong>Results: </strong>MMP2 and MMP9 mRNA levels were significantly higher in OKCs compared to oral mucosa (p < 0.05), with decreased mRNA levels after marsupialization. Gelatin zymography confirmed elevated gelatinase activity, particularly for MMP9, in OKC tissues. TLN1 and FBLN1 mRNA expressions were also elevated in OKCs, consistent with previous proteomic data, though not statistically significant. A significant correlation was observed between MMP9 mRNA expression and the total area of detached epithelium.</p><p><strong>Conclusion: </strong>MMP9 may play a critical role in epithelial detachment in OKCs and could serve as a therapeutic target or prognostic marker. Marsupialization appears to modulate matrix metalloproteinases expression, suggesting a molecular mechanism for its clinical benefits.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":"532-538"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892548","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":"Lymphatic Vessel Density or Area Are Not Reliable Prognostic Factors in Oral Cancer.","authors":"Ida Andersson Cronblad, Cathrine Elise Warvik, Inger-Heidi Bjerkli, Sonja Eriksson Steigen, Lars Uhlin-Hansen, Synnøve Norvoll Magnussen, Elin Hadler-Olsen, Anna Maria Wirsing","doi":"10.1111/jop.70148","DOIUrl":"https://doi.org/10.1111/jop.70148","url":null,"abstract":"<p><strong>Background: </strong>Oral tongue squamous cell carcinomas (OTSCC) frequently metastasise via lymphatic vessels, thus lymphangiogenesis may enhance tumour cell dissemination by increasing tumour-lymphatic interactions. The prognostic significance of lymphatic vessel density (LVD) and lymphatic vessel area (LVA) in OTSCC remains inconclusive. This study aimed to evaluate the association of tumour-associated LVD and LVA with clinical outcomes and pathological characteristics in a homogenous OTSCC cohort.</p><p><strong>Methods: </strong>We analysed tumour samples from 121 OTSCC patients using D2-40 immunohistochemical staining to visualise lymphatic vessels. We calculated mean LVD and LVA from five peritumoural hotspots per tumour and examined their relationships to clinical-pathological data including 5-year disease-specific survival (DSS) using cross-tabulation, Kaplan-Meier, and Cox regression analyses.</p><p><strong>Results: </strong>High LVD was more prevalent in well/moderately differentiated compared to poorly differentiated tumours (78.1% and 45.5%, respectively, p = 0.017). No significant associations were found between LVD or LVA and other clinical-pathological variables. Neither low LVD nor LVA significantly impacted 5-year DSS in univariate (HR = 0.65 CI: 0.32, 1.31; HR = 0.69, 95% CI: 0.34, 1.40, respectively) or multivariate analyses (HR = 0.75, 95% CI: 0.32, 1.76; HR = 0.54, 95% CI: 0.23, 1.25, respectively).</p><p><strong>Conclusions: </strong>LVD and LVA did not predict prognosis in this OTSCC cohort. Further standardised studies investigating lymphatic vessels within the tumour microenvironment are necessary to better understand their role and potential prognostic significance.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774336","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":"Global Prevalence of Oral Potentially Malignant Disorders: An Updated Systematic Review and Meta-Analysis.","authors":"Nicole Lonni, Tulio Silva Rosa, Camilla Kammer Pereira, Gilberto Melo, Saman Warnakulasuriya, Eliete Neves Silva Guerra, Elena Riet Correa Rivero","doi":"10.1111/jop.70146","DOIUrl":"https://doi.org/10.1111/jop.70146","url":null,"abstract":"<p><strong>Background: </strong>Oral potentially malignant disorders (OPMDs) represent a diverse group of mucosal disorders with varying risks of progression to oral cancer.</p><p><strong>Objective: </strong>This updated systematic review (SR) and meta-analysis (MA) estimated the global prevalence of histopathologically confirmed OPMDs, excluding oral lichen planus and lichenoid lesions.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted using predefined eligibility criteria. A total of 108 studies were included, comprising 86 additional studies and 22 from a previous SR.</p><p><strong>Results: </strong>The overall pooled prevalence of OPMDs was 4.67% (95% CI: 3.62-5.84). Prevalence of OPMDs was as follows: Asia (5.44%), followed by South America/Caribbean (5.21%), and Europe (4.89%). Considering OPMD cases, the proportion was higher among males (62.87%) and individuals aged ≥ 50 years (68.1%). Histopathological evidence of epithelial dysplasia was present in 46.21% of cases. Oral leukoplakia (OL), oral submucous fibrosis (OSMF), and actinic cheilitis (AC) emerged as the most prevalent lesions, with relevant differences considering the geographic regions. OL and OSMF were the most common OPMDs in Asia, while OL and AC predominated in South America/Caribbean, and in Europe OL remains the most frequently encountered OPMD.</p><p><strong>Conclusions: </strong>The global prevalence of OPMDs, estimated at approximately 5%, should be interpreted as a broad summary measure, given the substantial heterogeneity driven by regional variations possibly related to behavioral, biological, and/or environmental risk factors. Future preventive efforts should focus on the type of OPMD prevalent in the region/country. The heterogeneity across studies highlights the need for standardized, population-based studies using WHO nomenclature to better define the global burden.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774299","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":"Hemidesmosomal Proteins in Oral Cancer Progression: An Immunohistochemical Study of Human and Mouse.","authors":"Nikhil Mongia, Ali Ibrahim Mohammed, Michael McCullough, Rita Paolini, James A Rickard, Massimo Mascolo, Silvia Varricchio, Lorraine A O'Reilly, John Silke, Nicola Cirillo, Antonio Celentano","doi":"10.1111/jop.70145","DOIUrl":"https://doi.org/10.1111/jop.70145","url":null,"abstract":"<p><strong>Background: </strong>Hemidesmosomal subunits have gained attention for their potential role in the progression of oral squamous cell carcinoma (OSCC). However, formal analysis of quantitative expression patterns correlating with OSCC disease pathogenesis remains limited. This study evaluated the expression of key yet overlooked hemidesmosomal subunits, plectin isoform Ia (PIa), dystonin, and CD151 antigen, from normal tissue as well as tissue from hyperplasia, dysplasia, and OSCC in the human and murine oral cavity.</p><p><strong>Methods: </strong>Immunohistochemistry was performed on custom-built human tissue microarrays and 4-Nitroquinoline 1-oxide (4-NQO)-induced murine OSCC covering the spectrum of histological changes from normal to cancer. Quantitative image analysis of subunit expression was conducted using QuPath, with distinct analytical approaches applied to human tissues, including a refined method focusing on the basement membrane zone (BMZ) and adjacent basal epithelial layers, key sites of hemidesmosomal protein localization.</p><p><strong>Results: </strong>A significant increase in expression of all three proteins was observed comparing normal tissue with hyperplasia, dysplasia, and OSCC in murine tissues, but not in humans. The expression of hemidesmosomal proteins increased across this spectrum, suggesting their potential as progression biomarkers in mice. A focused analysis of the basement membrane zone and adjacent basal epithelial layers in human tissues revealed a sustained baseline expression and a significant reduction in CD151 antigen in OSCC compared with control and high-grade dysplasia groups, as well as a significant reduction in dystonin expression in OSCC compared to high-grade dysplasia.</p><p><strong>Conclusion: </strong>Our findings highlight the importance of biologically targeted region-of-interest selection when assessing hemidesmosomal protein expression in OSCC while demonstrating that BMZ-focused digital analysis provides a more informative approach for exploratory evaluation of heterogeneous human tissues alongside progression-associated patterns observed in a murine model.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729353","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":"Transcriptome Analysis and Histological Validation Identified the HO-1-u-1 Cell Line as a Model for Perineural Invasion in Oral Squamous Cell Carcinoma.","authors":"Taisuke Hani, Tomoo Kudo, Toshiki Nishimura, Yuuichi Soeno","doi":"10.1111/jop.70143","DOIUrl":"https://doi.org/10.1111/jop.70143","url":null,"abstract":"<p><strong>Background: </strong>Perineural invasion (PNI) is a pathological feature of oral squamous cell carcinoma (OSCC) that is associated with a poor prognosis. However, the molecular mechanisms remain poorly understood. The aim of this study was to establish an in vivo model to explore PNI in OSCC.</p><p><strong>Methods: </strong>We performed an integrated analysis of The Cancer Genome Atlas transcriptome data from tongue squamous cell carcinoma (TSCC) and floor of the mouth squamous cell carcinoma (FOMSCC) by the presence of PNI and identified differentially expressed genes (DEGs). We also performed xenografts of five OSCC cell lines (OSC19, OSC20, HSC2, KOSC2, and HO-1-u-1) into nude mouse tongues and assessed PNI histology. Furthermore, transcriptome profiles of the cell lines were analyzed to identify cell line-specific genes associated with PNI.</p><p><strong>Results: </strong>Among OSCCs, PNI cases were more prevalent in TSCC and FOMSCC. Expression analysis detected 103 DEGs in TSCC and 401 in FOMSCC. In TSCC, 42.2% of the DEGs were non-coding RNAs, whereas DEGs in FOMSCC were predominantly protein-coding genes enriched in pathways related to muscle contraction and fibrosis. Xenograft analysis revealed that HO-1-u-1 uniquely exhibited a nerve-directed invasion phenotype. Transcriptome analysis of OSCC cell lines demonstrated that HO-1-u-1 was enriched in neural- and glial-related pathways, consistent with its neurotropic behavior in vivo.</p><p><strong>Conclusions: </strong>Our transcriptome analysis suggested that different pathways might drive PNI in TSCC and FOMSCC, depending on their origin. We also demonstrated that HO-1-u-1 is a unique OSCC cell line with strong neurotropic properties and a valuable xenograft model for OSCC PNI.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729316","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":"Prognostic Significance of CD105-Assessed Angiogenesis in Relation to Survival and Clinicopathological Features of Oral Squamous Cell Carcinoma.","authors":"Amol Ramchandra Gadbail, Minal Chaudhary, Satyajit Ashok Tekade, Alka Hande, Monal Yuwanati, Pranali Nimonkar, Shailesh M Gondivkar, Sachin Sarode","doi":"10.1111/jop.70142","DOIUrl":"https://doi.org/10.1111/jop.70142","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to determine the clinical significance of mean vascular density (MVD) using the expression of CD105 (endoglein) to predict the 3- and 5-year survival rates of oral squamous cell carcinoma (OSCC), as well as assess its value for predicting clinical outcomes of OSCC.</p><p><strong>Methods: </strong>A total of 217 OSCC patients treated surgically between 2010 and 2015 were included. Immuno-histochemistry for CD105 was performed, and MVD was quantified. The correlations of MVD with histopathological (HSPL) grade, the clinical Tumor Node Metastasis (TNM) stage, nodal status and survival were analyzed. Multivariate Cox proportional hazards regression analysis was also performed.</p><p><strong>Results: </strong>The MVD significantly increased with increasing HSPL grade from well-differentiated OSCC to poorly-differentiated OSCC (p < 0.001). MVD was significantly increased for advanced-stage TNM cases (III/IV) and metastatic cases when compared to early-stage and non-metastatic tumors (p < 0.001). Survival analysis revealed an inverse relationship between MVD and both three- and five-year disease-free survival. Patients with low MVD had the highest disease-free survival (3 years: 96.2%, 5 years: 92.7%), whereas those with high MVD had poor survival (3 years: 34.0%, 5 years: 27.9%). Multivariate Cox regression analysis confirmed MVD and HSPL grade as independent prognostic factors for overall survival.</p><p><strong>Conclusion: </strong>An elevated MVD by CD105 expression is strongly correlated with aggressive HSPL features, stage, nodal metastasis, and poor prognosis in OSCC. In addition to prognostic information, CD105 has the potential to be a target for anti-angiogenic strategies in OSCC indicating its potential use in clinical risk stratification and planning.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729335","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":"Effect of miR-214-3p on Cisplatin Resistance in Oral Squamous Cell Carcinoma by Regulating Ferroptosis Through Targeting GPX4.","authors":"Rongxia Zhang, Jing Zhang, Yongle Qiu, Alin Tian, Weiwei Yin, Nan Zhang, Yang Liu, Yunfang Bai","doi":"10.1111/jop.70138","DOIUrl":"https://doi.org/10.1111/jop.70138","url":null,"abstract":"<p><strong>Introduction: </strong>Emerging evidence underscores the potential of ferroptosis as a promising therapeutic target in cancer. However, the role of microRNAs (miRNAs) in modulating ferroptosis sensitivity remains largely unexplored, particularly in the context of oral squamous cell carcinoma (OSCC) chemoresistance. This study was designed to investigate the role of miR-214-3p in regulating ferroptosis by targeting glutathione peroxidase 4 (GPX4) and its influence on cisplatin (DDP) resistance in OSCC.</p><p><strong>Methods: </strong>Patients diagnosed with OSCC and receiving DDP-based chemotherapy between February 2022 and February 2024 at our institution were included in this study. Expression levels of miR-214-3p and GPX4 were quantitatively assessed in DDP-sensitive versus DDP-resistant OSCC tissues and cell lines using qRT-PCR and Western blot. Cell viability, IC50 values, and apoptosis were evaluated using the CCK-8 assay and flow cytometry. Intracellular reactive oxygen species (ROS) and Fe²⁺ levels were measured to determine the status of ferroptosis. Bioinformatics prediction and dual-luciferase reporter assays confirmed the interaction between miR-214-3p and GPX4. In vivo xenograft models were utilized to investigate the impact of miR-214-3p on OSCC tumor growth.</p><p><strong>Results: </strong>As an initial assessment of clinical relevance, miR-214-3p was significantly downregulated in DDP-resistant OSCC tissues and cells, whereas GPX4 expression was markedly upregulated. Overexpression of miR-214-3p substantially decreased cell viability, reduced the IC₅₀ values of DDP, and promoted apoptosis in resistant cells. In comparison to parental cells, resistant cells demonstrated lower levels of ROS and Fe²⁺. Overexpression of miR-214-3p or treatment with a ferroptosis inducer (Erastin) increased ROS and Fe²⁺ levels, an effect that was effectively reversed by a ferroptosis inhibitor (Ferrostatin-1). Bioinformatics analysis combined with luciferase reporter assays confirmed the direct binding of miR-214-3p to the 3' untranslated region (UTR) of GPX4. The overexpression of miR-214-3p resulted in the downregulation of GPX4, whereas overexpression of GPX4 reversed the effects mediated by miR-214-3p. Additionally, the overexpression of miR-214-3p in xenograft models inhibited tumor growth, which was correlated with decreased GPX4 expression and increased sensitivity to DDP.</p><p><strong>Conclusion: </strong>Our findings reveal a novel miR-214-3p/GPX4/ferroptosis axis in OSCC DDP resistance. miR-214-3p suppresses GPX4 to promote ferroptosis, thereby reversing DDP resistance. This study identifies miR-214-3p as a potential therapeutic target for overcoming chemoresistance in OSCC by modulating ferroptosis.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698873","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}