American journal of cancer research最新文献

{"title":"Establishment and validation of a recurrence risk model in early-stage tongue squamous cell carcinoma patients incorporating immune-inflammatory biomarkers and clinicopathological parameters.","authors":"Xiangxiang Liao, Hongwen Wu, Hui Yang, Xiaoting Pan, Wei Wu, Ke Xu, Yanghong Xu, Yaling Chen, Xiangcheng Liu, Mengcheng Liu, Hui Li, Hui Huang","doi":"10.62347/CMXU1610","DOIUrl":"10.62347/CMXU1610","url":null,"abstract":"<p><strong>Objective: </strong>To develop and validate a machine learning-based predictive model incorporating immuno-inflammatory biomarkers and clinicopathological parameters to predict recurrence risk in early-stage tongue squamous cell carcinoma (TSCC) patients.</p><p><strong>Methods: </strong>This retrospective study included 515 early-stage TSCC patients treatment at Xinyu People's Hospital between May 2014 and May 2019. Medical records and laboratory data were reviewed. Patients were randomly divided into a training cohort (n=339) and a validation cohort (n=176). Feature selection was performed using LASSO, Xgboost, and Support Vector Machine (SVM) algorithms to identify key features associated with recurrence. A predictive nomogram was then built based on multivariate Cox regression analysis. Model performance was evaluated using receiver operating characteristic (ROC) curve analysis, calibration plots, and decision curve analysis (DCA).</p><p><strong>Results: </strong>Recurrence was observed in 160 cases (31.07%), with 111 (32.74%) in training cohort (n=339) and 49 (27.84%) in the validation cohort (n=176). Machine learning algorithms identified several key risk factors for recurrence, including immuno-inflammatory markers (e.g., white blood cell count [WBC], platelet count [PLT], C-reactive protein [CRP], neutrophil-to-lymphocyte ratio [NLR], systemic inflammation response index [SIRI], C-reactive protein-to-albumin ratio [CAR]) and clinicopathological characteristics (e.g., pathological classification, chemotherapy status, tumor location). The nomogram achieved areas under the ROC curve (AUCs) of 0.902 (95% CI: 0.866-0.937) in the training set and 0.819 (95% CI: 0.759-0.876) in the validation set. Calibration curves demonstrated good predictive consistency (P=0.621). DCA showed a clear net clinical benefit across a wide range of thresholds probabilities (P<0.001).</p><p><strong>Conclusion: </strong>This predictive model, integrating immuno-inflammatory markers and clinicopathological features, exhibits excellent predictive performance for recurrence risk in early-stage STCC and offers substantial clinical utility.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 7","pages":"2970-2987"},"PeriodicalIF":2.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854222","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":"Development and validation of nomogram models for predicting urinary incontinence following radical prostatectomy in high-risk prostate cancer patients.","authors":"Kaiqiang Chen, Weihua Liu, Jian Wu, Renqiang He, Shanghuan Xie, Yaowu Su","doi":"10.62347/ZYAA3728","DOIUrl":"10.62347/ZYAA3728","url":null,"abstract":"<p><strong>Objective: </strong>To develop a risk stratification model for predicting urinary incontinence following radical prostatectomy (RP) in high-risk prostate cancer patients based on their clinicopathological characteristics.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 520 prostate cancer patients who underwent RP between January 2016 and January 2024. Baseline characteristics, pathological data, laboratory parameters, and surgery-related factors were collected. Urinary continence status at 1, 3, and 6 months postoperatively was assessed. Multivariate logistic regression analyses were performed to identify independent risk factors, and nomograms were constructed to predict urinary incontinence risk at each time point.</p><p><strong>Results: </strong>Urinary incontinence rates at 1, 3, and 6 months postoperatively were 92.88%, 69.62%, and 23.65%, respectively. At 1 month, a higher Gleason score (OR=2.178, P=0.003) was a risk factor, while robot-assisted surgery was protective (OR=0.289, P=0.003). At 3 months, higher Gleason score (OR=1.565, P=0.004) increased risk, whereas lower BMI (<25 kg/m²) (OR=0.448, P=0.005) and longer preoperative membranous urethral length (≥14 mm) (OR=2.368, P<0.001) were protective. At 6 months, shorter membranous urethral length (<14 mm) (OR=3.622, P<0.001), neoadjuvant hormone therapy (OR=5.783, P<0.001), and higher Gleason score (OR=2.824, P<0.001) were risk factors, while lower BMI (OR=0.317, P<0.001), smaller prostate volume (<40 mL) (OR=0.591, P=0.044), and lower CONUT score (<4) (OR=0.372, P<0.001) were protective. The nomograms showed good predictive performance, with AUCs of 0.679 at 3 months and 0.818 at 6 months.</p><p><strong>Conclusions: </strong>The developed nomograms effectively stratify the risk of urinary incontinence following RP in high-risk patients, facilitating individualized perioperative management and rehabilitation strategies.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 7","pages":"3017-3034"},"PeriodicalIF":2.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854172","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":"KRAS mutation subtypes in metastatic non-small cell lung cancer.","authors":"Ali Aytac, Bilgin Demir, Onur Yazdan Balcik, Tuba Ugur Tuzcu, Esin Oktay, Ibrahim Halil Erdogdu, Ozgur Tanriverdi, Ozan Yazici","doi":"10.62347/GYHT4724","DOIUrl":"10.62347/GYHT4724","url":null,"abstract":"<p><p>The aim of this study is to determine the clinicopathologic features of KRAS mutant metastatic non-small cell lung cancer (NSCLC) patients and to determine the clinical, prognostic and survival differences between subtypes and their relationship with response to treatment. A total of 101 patients with KRAS mutant metastatic non-small cell lung cancer treated in 3 oncology centers between 2013 and 2024 were included in this retrospective, multicenter study conducted in Turkey. Molecular analysis was confirmed by next generation sequencing (NGS; QIAGEN Clinical Insight Interpretation, United States). The Kaplan-Meier method was used to compare progression-free (PFS) and overall survival (OS) times between KRAS subgroups. KRAS G12C mutation was detected in 69 (68.3%) and KRAS non-G12C mutation in 32 (31.7%) patients. In both groups, the majority of patients were male (91.3% vs. 84.4%), smokers or former smokers (92.8% vs. 90.6%) and histologically had adenocarcinoma subtype (88.4% vs. 81.3%). There was no statistically significant difference in PD-L1 expression (21.7% vs. 34.4%, P: 0.132). In the KRAS non-G12C group, the most common mutations were G12V 15 (14.8%) and G12D 6 (5.9%). The most common co-mutation accompanying KRAS G12C mutation was TP53 (23%), while the most common co-mutation accompanying KRAS non-G12C was Rictor (36.3%). While 23 (33.3%) patients with KRAS G12C mutation developed brain metastasis, this rate was 14 (43.8%) in the KRAS non-G12C mutation group (P=0.312). Median follow-up was 15.30 (0.3-112.0) months. The objective response rate (ORR) with first-line treatment was 47.5% in the KRAS G12C group and 48.3% in the KRAS non-G12C group (P: 0.657). Median PFS was 4.46 (2.85-6.08) months in the KRAS G12C group and 5.23 (3.46-6.99) months in the KRAS non-G12C group (P: 0.852). Median overall survival was 14.46 (8.34-20.58) months in the KRAS G12C group and 15.36 (5.01-25.71) months in the KRAS non-G12C group (P: 0.201). In KRAS mutant metastatic NSCLC patients, no significant difference was found between KRAS subtypes (G12C vs. non-G12C) in terms of clinical, prognostic and survival data.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 7","pages":"3188-3196"},"PeriodicalIF":2.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854226","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":"Enhanced inhibitory effects of mianserin in combination with sorafenib on liver cancer growth through targeting the CCR9-AKT pathway.","authors":"Ya-Hui Huang, Chia-Jung Liao, Meng-Han Wu, Ming-Wei Lai, Yung-Hsin Yeh, Chau-Ting Yeh, Yang-Hsiang Lin, Kwang-Huei Lin","doi":"10.62347/CYDE4091","DOIUrl":"10.62347/CYDE4091","url":null,"abstract":"<p><p>Previously, our group showed that mianserin, an atypical antidepressant, exerts stronger cytotoxicity against liver cancer cells than normal hepatocytes, supporting its potential application as a therapeutic agent for liver cancer. However, the anti-tumor effects of mianserin <i>in vivo</i> and its mechanisms are yet to be established. In this study, we explored the inhibitory effects and mechanisms of mianserin and evaluated its efficacy in combination with sorafenib against liver cancer cells. Effects on cell viability were assessed via MTT and flow cytometry assays and antitumor activity evaluated using a xenograft model. Changes in the expression and distribution of specific proteins within cells were examined via immunoblot assay. Our results indicate that mianserin exerts cytotoxic effects by inhibiting cell viability through suppression of proliferation and induction of apoptosis. Therapeutic effects of mianserin were validated via intratumoral injection in the xenograft model. Mechanistically, our data indicate that mianserin-induced cytosolic HSP60 translocates to cell surface and participates in the downregulation of CCR9, leading to inactivation of the AKT-(β-catenin/NFκB) signaling pathway. Combination treatment with mianserin and sorafenib induced significant synergistic effects on cell viability, apoptosis, and <i>in vivo</i> tumor growth in both parental and sorafenib-resistant liver cancer cells. This study is the first to demonstrated that mianserin effectively limits the growth of liver cancer by downregulating CCR9, in turn, inactivating the AKT-(β-catenin/NFκB) pathway. Both <i>in vitro</i> and <i>in vivo</i> experiments highlight mianserin's potential as an adjuvant therapy to sorafenib, offering a promising strategy to overcome current challenges in liver cancer treatment.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 6","pages":"2890-2904"},"PeriodicalIF":3.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641498","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":"ESRP1 drives subtype-specific breast cancer progression through ER-regulated transcriptional programs and EMT-related splicing switch.","authors":"Xinyi Wang, Shuping Song, Weixuan Lin, Jiandi Huang, Wenchao Zhong, Donghang Li, Cainan Huo, Yongxuan Wang, Dingke Chen, Zhi Zhang, Yanqin Sun","doi":"10.62347/OXPE5390","DOIUrl":"10.62347/OXPE5390","url":null,"abstract":"<p><p>Epithelial Splicing Regulatory Protein 1 (ESRP1), an epithelial splicing regulator, influences the invasiveness and metastasis of breast cancer cells, yet its prognostic significance and interaction with estrogen receptors are not fully understood. Our findings indicate that ESRP1 is significantly up-regulated in breast cancer tissues and correlates positively with adverse clinical outcomes, particularly in estrogen receptor (ER) positive breast cancer. In vitro experiments with cells demonstrated a dual regulatory mechanism: in ER-positive breast cancer cells, reduced expression of ESRP1 suppresses tumor cell proliferation but does not significantly affect tumor cell invasion and migration; conversely, in ER-negative breast cancer cells, ESRP1 hinders tumor progression by regulating the alternative splicing of epithelial-mesenchymal transition (EMT)-related genes. To investigate whether the presence of ER is a decisive factor in ESRP1's role, we treated ER-positive breast cancer cells with an ER inhibitor to induce EMT, followed by the knockdown of ESRP1, which further promoted the EMT process and enhanced the cells' invasive and migratory abilities. This study demonstrates that ESRP1 is a potential breast cancer prognostic marker with subtype specificity and its value as a molecular target needs to be accurately assessed in the context of breast cancer subtypes, as ESRP1 function may be highly dependent on the ER background.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 6","pages":"2807-2825"},"PeriodicalIF":3.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641501","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":"Resistance patterns of non-small cell lung cancer treated with third-generation epidermal growth factor receptor-tyrosine kinase inhibitors.","authors":"Nana Chen, Feng Zhao, Lu Yang, Xiaojing Tan, Dongfeng Wang, Xin Ye, Zhigang Wei","doi":"10.62347/ANQD9699","DOIUrl":"10.62347/ANQD9699","url":null,"abstract":"<p><p>The third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the preferred therapy for patients with EGFR mutant non-small cell lung cancer (NSCLC); however, the therapy faces resistance challenges. We aimed to clarify the resistance patterns of EGFR-TKIs in patients with EGFR mutant NSCLC. In this retrospective study, we analyzed 104 patients with advanced EGFR mutant NSCLC who experienced treatment failure of third-generation EGFR-TKIs. Resistance models were classified as 1) original site failure (OF), distant site failure (DF), and combined failure (ODF) based on the failure site or 2) oligo-progression (OP) and non-oligoprogression based on the disease progression (PD) pattern. Among the patients, 58.7% (n = 61 of 104) developed OF, while 25 (24.0%) and 18 (17.3%) developed DF and ODF, respectively. A high OP rate (76.9%, n = 80) was observed, with primary progression accounting for 30.8%. OF was related to sex (odds ratio = 3.961, 95% confidence interval: 1.629-9.631, P = 0.002). Over 50% of patients with third-generation EGFR-TKI treatment failure developed OF. Sex, central nervous system metastases, and disease stage influenced the resistance patterns of the EGFR-TKI therapy.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 6","pages":"2843-2854"},"PeriodicalIF":3.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641518","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":"Splicing factor 3b subunit 4 (SF3b4) is mediated by EP300 and CREBBP to promote colorectal cancer (CRC) proliferation by enhancing autophagy.","authors":"Tianhao Wu, Zhongxiang Xiao, Bowen Su, Zaihua Yan, Yv Zhao, Cheng Huang, Lu Zhou, Hongpeng Tian, Guangjun Zhang","doi":"10.62347/AHXI2343","DOIUrl":"10.62347/AHXI2343","url":null,"abstract":"<p><p>Splicing factor 3b subunit 4 (SF3b4) is closely associated with cancer development. As a core subunit of the SF3b complex, SF3b4 participates in regulating alternative splicing, and its abnormal expression is linked to the onset of malignant tumors. However, the role of SF3b4 in colorectal cancer (CRC) remains undefined. This study demonstrates that in CRC, E1A binding protein p300 (EP300) and CREB binding protein (CREBBP) regulate SF3b4 expression by activating Histone H3 lysine 27 acetylation (H3K27ac) on the SF3b4 promoter. Additionally, enhanced autophagy counteracts the proliferation-inhibitory effect of SF3b4 knockdown in CRC cells. Implications Statement: SF3b4 may promote CRC proliferation by enhancing cellular autophagy. SF3b4 acts as a potential oncogene in CRC tumorigenesis and progression. SF3b4 serves as a promising prognostic biomarker for CRC.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 6","pages":"2826-2842"},"PeriodicalIF":3.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641520","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":"Identification of CDK2 as a key apoptotic gene for predicting cervical cancer prognosis using bioinformatics and machine learning.","authors":"Miao-Miao Li, Min Song, Shu-Xia Wu, Xing-Ye Ren","doi":"10.62347/RUXJ3980","DOIUrl":"10.62347/RUXJ3980","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to identify apoptosis - related genes with diagnostic and prognostic value in cervical cancer (CC) using integrated bioinformatics and machine learning approaches.</p><p><strong>Methods: </strong>Gene expression datasets were obtained from the National Center for Biotechnology Information Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA), with GSE192897 used as the training set. A total of 451 differentially expressed genes (DEGs) were identified, including 221 upregulated and 230 downregulated genes. Eleven apoptosis - related upregulated DEGs were selected for further analysis using three machine learning algorithms: random forest, logistic regression, and support vector machine. Validation was performed using GSE192897, GSE166466, and TCGA-CESC datasets.</p><p><strong>Results: </strong>Among the evaluated genes, cyclin-dependent kinase 2 (CDK2) consistently achieved an AUC > 0.8 in all three validation datasets and had a weighted sum rank > 10, meeting stringent selection criteria. In a CC mouse model, CDK2 expression was significantly elevated and positively correlated with squamous cell carcinoma antigen, carcinoembryonic antigen, vascular endothelial growth factor, and heparanase. siRNA-mediated knockdown of CDK2 reduced cell proliferation and migration while promoting apoptosis. Mice with high CDK2 expression showed significantly lower 4-week survival rates, indicating poor prognosis.</p><p><strong>Conclusions: </strong>This study identified CDK2 as a key apoptosis - related gene with strong diagnostic and prognostic value in cervical cancer. CDK2 promotes tumor progression and is associated with poor survival, suggesting its potential as a biomarker and therapeutic target for personalized treatment strategies in CC.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 6","pages":"2750-2764"},"PeriodicalIF":3.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641462","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":"Are they all the same? Different effects of opioid types on survival in metastatic NSCLC receiving nivolumab.","authors":"Onur Yazdan Balçık, İsmail Beypınar, Semiha Urvay, Müslih Ürün, Berrak Erçek, Canan Yıldız, Murat Araz, Ahmet Oruç, Yusuf İlhan, Arif Hakan Önder, Hacer Demir","doi":"10.62347/VHDF3303","DOIUrl":"10.62347/VHDF3303","url":null,"abstract":"<p><p>The aim of this study was to evaluate the effects of concurrent opioid analgesic (OA) use and types of OA on progression-free survival (PFS) and overall survival (OS) in non-small cell lung cancer (NSCLC) patients receiving nivolumab. This observational, retrospective study included patients with pathologically confirmed, driver mutations negative metastatic NSCLC at five different hospitals in Turkey between 2018 and 2024. A total of 209 patients were included in this study. Of these patients, 113 (54.1%) used OA. 86 (41.1%) patients were using tramadol, and 48 (23.4%) were using fentanyl. The median survival of the group without OA was significant in the univariate analysis compared to that of the group with OA PFS (7 vs. 4 months, P = 0.006) an OS (8 vs. 14 months, P = 0.003). The group with bone metastases had worse OS than the group without bone metastases [7 vs. 15 months, HR (95% CI) = 1.810 (1.064-3.079), (P = 0.029)]. In the group without bone metastases, patients on tramadol had worse PFS than patients not on tramadol [5 vs. 8 months, HR (95% CI) = 2.260 (1.097-4.655), (P = 0.027)]. In conclusion, OA use was associated with poor PFS and OS. Fentanyl use led to worse OS in the group with bone metastases, whereas tramadol use led to worse PFS in the group without bone metastases. The prognostic impact of OA may differ according to the site of metastasis; therefore, prospective studies that include the type of OA are needed.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 6","pages":"2794-2806"},"PeriodicalIF":3.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641489","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":"METTL3-mediated m⁶A methylation of lncRNA PVT1 promotes the progression of oral squamous cell carcinoma via the miR-185-5p/SERPINB4 axis.","authors":"Cheng Chen, Jun Li, Bingwu Yang, Li Kong, Di Zhang, Jianran Guo, Longxun Zhou, Guangliang Bai, Huaqiang Zhao, Zhen Meng","doi":"10.62347/HERV8396","DOIUrl":"10.62347/HERV8396","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors of the head and neck region. Plasmacytoma variant translocation 1 (PVT1), a long non-coding RNA (lncRNA), has been found to be overexpressed in multiple cancers, including OSCC. However, the upstream and downstream regulatory mechanisms through which PVT1 influences the malignant progression of OSCC remain to be further explored. In this study, PVT1 was confirmed to be overexpressed in OSCC tissues, and its roles in promoting OSCC cell proliferation, migration and invasion were identified. RNA-sequencing was used to screen the candidate target genes of PVT1, among which serpin family B member 4 (SERPINB4) was the most downregulated. SERPINB4 promoted OSCC cell proliferation, migration and invasion. In addition, mechanistic investigations demonstrated that PVT1 regulates SERPINB4 by sponging miR-185-5p in OSCC cells. Furthermore, SERPINB4 overexpression or miR-185-5p knockdown partly restores the decrease of OSCC cell proliferation and metastasis induced by PVT1 knockdown. Additional studies revealed that methyltransferase-like 3 (METTL3)-mediated N6-methyladenosine (m⁶A) modification induced the upregulation of PVT1 by stabilizing its RNA transcript. In conclusion, elevated expression of PVT1 in OSCC is associated with poor prognosis and promotes tumor development. METTL3 promotes PVT1 stability through m⁶A deposition and upregulates its expression in OSCC, which could upregulate SERPINB4 by sponging miR-185-5p, and ultimately promoting OSCC growth and metastasis. These findings suggest that PVT1 could serve as a potential biomarker and therapeutic target for OSCC.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 6","pages":"2872-2889"},"PeriodicalIF":3.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641469","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}