Translational cancer research最新文献

{"title":"Multimodal approach for the comprehensive management of non-small cell lung cancer: a case report.","authors":"Jincai Zhou, Kai Ma, Xinpeng Han, Wenhai Li","doi":"10.21037/tcr-2025-aw-2311","DOIUrl":"https://doi.org/10.21037/tcr-2025-aw-2311","url":null,"abstract":"<p><strong>Background: </strong>Lung squamous cell carcinoma (LSCC) is a common malignant tumor with a high incidence rate and poses a serious threat to patients' health and quality of life. This case reports the complex diagnosis and treatment process of a patient with LSCC of the right upper lobe, which has important clinical research value.</p><p><strong>Case description: </strong>The patient was diagnosed with LSCC of the right upper lobe in January 2024, and attended the hospital 4 months after stent implantation in the right main bronchus. In 2024, the patient was diagnosed with moderately differentiated LSCC of the right upper lobe (T2N3M0, stage IIIB). After three cycles of chemotherapy combined with immunotherapy, the patient underwent sleeve resection of the upper lobe of the right lung when tumor was downgraded. Following the operation, the patient developed pulmonary infection and immune-related pneumonitis. His condition was relieved after various anti-infection treatments and hormone intervention. Postoperatively, the patient developed anastomotic stenosis, which was initially managed with the implantation of a silicone stent. The subsequent course was complicated by a pan-drug-resistant <i>Acinetobacter baumannii</i> infection, contributing to restenosis and necessitating stent exchange to a covered metal stent. The etiological examination revealed pan-drug-resistant <i>Acinetobacter baumannii</i> infection. After adjusting the treatment plan based on the drug sensitivity results, the infection was effectively controlled. Following confirmation of airway healing, the stent was successfully removed. At present, the patient's respiratory symptoms have improved, and his activity endurance has increased.</p><p><strong>Conclusions: </strong>This case demonstrates the complexity of multi-stage treatment, including chemotherapy, surgery, anti-infection and immunotherapy, for a patient with LSCC of the right lobe, accompanied by multiple complications. Bronchial stent implantation and adjustment significantly improved the airway obstruction, while the precise anti-infection strategy based on etiology effectively controlled the infection. Consideration of factors such as the patient's smoking history had an important impact on the development of the disease and the therapeutic effect.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 3","pages":"221"},"PeriodicalIF":1.7,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular classification and construction of prognostic risk model via machine learning based on metabolic-related genes in hepatocellular carcinoma.","authors":"Hongkang Wang, Yonghao Li, Huayu Zhang, Yaozhong Ping, Wan Zhang, Ying'ao Chen, Bing Han","doi":"10.21037/tcr-2025-aw-2444","DOIUrl":"https://doi.org/10.21037/tcr-2025-aw-2444","url":null,"abstract":"<p><strong>Background: </strong>Despite recent advances in therapeutic strategies for hepatocellular carcinoma (HCC), patient prognosis remains unsatisfactory. Accumulating evidence indicated that dysregulation of metabolism-related pathways and genes plays a pivotal role in HCC progression. Accordingly, metabolic-associated genes hold promise as prognostic biomarkers and potential predictors of therapeutic response. This study aimed to identify distinct metabolic subtypes of HCC and compare their clinicopathological and genomic features. Prognosis-associated metabolic genes were screened using an integrated machine learning framework, from which a risk-scoring model was constructed to simultaneously predict HCC prognosis and immunotherapy response.</p><p><strong>Methods: </strong>A systematic evaluation of metabolic patterns was conducted to elucidate the association between metabolism and HCC. To establish a prognostic and therapeutic prediction model, we developed an integrative framework based on machine learning algorithms by using comprehensive profiling of RNA sequencing data. Subsequently, nine metabolic-related genes were identified, and their biological functions were validated with clinical characteristics, immune cell infiltration, and complicated cellular signaling pathways.</p><p><strong>Results: </strong>Two molecular clusters with distinct clinical and biological characteristics were identified in HCC. Utilizing the computational framework, a metabolic-based prognostic model was constructed, which exhibited superior prognostic accuracy and outperformed previously reported models. An efficient clinical nomogram integrating the risk score with clinicopathological variables was subsequently established. Metabolic status was found to be closely associated with immunological features, and the proposed algorithms effectively predicted immunotherapy responsiveness. Furthermore, the risk score demonstrated predictive power for drug sensitivity in HCC patients. A multilevel evaluation of prognosis-related metabolic genes confirmed the stability and robustness of the model.</p><p><strong>Conclusions: </strong>This study systematically demonstrated the relationship between metabolic alterations and HCC. We established a robust prognostic model which was capable of accurately predicting patient survival, prognosis, and therapeutic responses. This model held promise for improving clinical decision-making and advancing personalized treatment strategies in HCC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 3","pages":"147"},"PeriodicalIF":1.7,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CA9-related ferroptosis is a potential therapeutic target of kaempferol anti-oral squamous cell carcinoma.","authors":"Jia-Yi Lu, Xin-Miao Zhao, Xian-Bao Liu, Li Gao","doi":"10.21037/tcr-2025-1488","DOIUrl":"https://doi.org/10.21037/tcr-2025-1488","url":null,"abstract":"<p><strong>Background: </strong>Oral squamous cell carcinoma (OSCC) is the most common oral malignancy, affecting the tongue, palate, mouth floor, alveolar ridge, and buccal mucosa. Kaempferol, a natural flavonoid, exhibits anti-oral cancer properties, but its mechanisms remain unclear. This study aimed to investigate kaempferol's therapeutic potential and molecular mechanisms in OSCC using network pharmacology, molecular docking, and experimental validation.</p><p><strong>Methods: </strong>Kaempferol's components and targets were identified via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). OSCC-related genes were sourced from GeneCards and Gene Expression Omnibus (GEO) databases. Network and molecular docking analyses were performed using Cytoscape and Autodock, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using Database for Annotation, Visualization and Integrated Discovery (DAVID). <i>In vitro</i> and <i>in vivo</i> experiments validated kaempferol's effects.</p><p><strong>Results: </strong>Kaempferol induced ferroptosis, reducing OSCC cell viability and increasing apoptosis dose-dependently. Carbonic anhydrase IX (CA9) emerged as a core gene mediating kaempferol's anti-OSCC effects via ferroptosis. Molecular docking confirmed strong binding affinity between kaempferol and CA9 (-6.24 kcal/mol). GO and KEGG analyses revealed kaempferol's modulation of p53/FoxO/cellular senescence pathways. Experiments confirmed kaempferol's inhibition of OSCC proliferation and migration through CA9/ferroptosis induction.</p><p><strong>Conclusions: </strong>Kaempferol exerts anti-OSCC effects via CA9/ferroptosis, highlighting its potential as a therapeutic agent for OSCC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 3","pages":"179"},"PeriodicalIF":1.7,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-assembled structures of Fe₃O₄ nanoparticles for therapy of cervical cancer by inducing apoptosis and autophagy.","authors":"Sumiao Dong, Waner Liu, Dou Yu, Xian Zhang, Dailing Chen, Ting Wang","doi":"10.21037/tcr-2025-1-2741","DOIUrl":"https://doi.org/10.21037/tcr-2025-1-2741","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer is one of the most common cancers among women globally, and its treatments remain limited, urgently needing new strategies. In recent years, the use of enzyme-like Fe₃O₄ nanoparticles (NPs) has exhibited promising antitumor potential due to their unique physicochemical properties and biocompatibility. However, the therapeutic effect of Fe₃O₄ NPs is often limited by their surface hydrophobicity. Therefore, this study aimed to construct Fe₃O₄-CC3 co-assemblies to overcome surface hydrophobicity and enhance antitumor efficacy.</p><p><strong>Methods: </strong>Our study designed Fe₃O₄-CC3 co-assemblies through a unique oil-in-water (O/W) emulsion restriction strategy. Using HeLa cells as the experimental model, the effect of Fe₃O₄-CC3 on cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8) assay. Morphological changes were observed under an optical microscope. The impact of Fe₃O₄-CC3 on cell migration was assessed using the wound-healing assay, and the apoptosis rate was analyzed by flow cytometry. The protein levels of apoptosis protein (Caspase-3), autophagy protein (Beclin1, p62, and LC3-B), and PI3K/AKT/mTOR pathway were determined by Western blot. The expression level of LC3-B in cells was observed by confocal fluorescence microscopy. Anti-tumour activity of Fe₃O₄-CC3 co-assemblies was accessed by subcutaneous xeno-transplanted tumour model of human cervical cancer in nude mice.</p><p><strong>Results: </strong>Compared to traditional NPs, these co-assemblies are inherently hydrophobic, but they transition to a hydrophilic characteristic through the incorporation of the cationic surfactant (DTAB) via hydrophobic interactions. Our results demonstrated that Fe₃O₄-CC3 co-assemblies were superior to Fe₃O₄ NPs in inhibiting cell proliferation and migration. Flow cytometry and Western blot analyses indicated that Fe₃O₄-CC3 co-assemblies induced apoptosis by activating apoptosis-related proteins and inhibiting the PI3K/AKT/mTOR signaling pathway, exhibiting multiple anti-tumor mechanisms.</p><p><strong>Conclusions: </strong>Fe₃O₄-CC3 co-assemblies induced apoptosis and promoted autophagy, accompanied by the inactivation of PI3K/AKT/mTOR pathway in cervical cancer and further inhibited tumour growth, which may lead to new therapeutic choices for patients and promote the development of nanomedicine in cancer therapy.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 3","pages":"150"},"PeriodicalIF":1.7,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling glutamine metabolism in ovarian carcinoma: signaling cross-talk, positron emission tomography utility, and therapeutic boundaries.","authors":"Jiajia Tong","doi":"10.21037/tcr-2025-1-2920","DOIUrl":"https://doi.org/10.21037/tcr-2025-1-2920","url":null,"abstract":"","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 3","pages":"222"},"PeriodicalIF":1.7,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quetiapine inhibits the oxidative phosphorylation in head and neck squamous cell carcinoma through suppressing NAT10-mediated ac4C modification.","authors":"Shanshan Du, Min Mao, Wanfen Wang, Xiaoming Xu, Shuang Ye, Longchuan Xie","doi":"10.21037/tcr-2025-1-2683","DOIUrl":"https://doi.org/10.21037/tcr-2025-1-2683","url":null,"abstract":"<p><strong>Background: </strong>N4-acetylcytidine (ac4C) is an RNA epigenetic modification, newly discovered to be catalyzed by the enzyme N-acetyltransferase 10 (NAT10). This study aimed to elucidate the functional role and regulatory mechanism of NAT10-mediated ac4C RNA modification in head and neck squamous cell carcinoma (HNSCC), and to explore its potential as a druggable target.</p><p><strong>Methods: </strong>Bioinformatics analysis of The Cancer Genome Atlas (TCGA) data was performed to assess NAT10 expression and its clinical correlation in HNSCC. Gene set enrichment analysis (GSEA) was conducted on differentially expressed genes from NAT10-high versus NAT10-low patients. The L1000 FireWorks Display (L1000FWD) platform was utilized to predict potential NAT10-targeting drugs. The anti-tumor effects and mechanisms of the top candidate, quetiapine, were validated through <i>in vitro</i> experiments, including binding assays, functional phenotyping (proliferation, migration, and apoptosis), and assessment of mitochondrial function via oxygen consumption rate (OCR) measurements.</p><p><strong>Results: </strong>NAT10 was significantly upregulated in HNSCC, and its high expression was correlated with advanced tumor stage, higher grade, poor overall survival, and specific immune cell infiltration patterns. GSEA revealed a strong association between NAT10 and the oxidative phosphorylation (OXPHOS) pathway. Quetiapine was identified as a top candidate targeting the NAT10-associated signature. <i>In vitro</i> experiments confirmed that quetiapine directly bound to NAT10, inhibited its expression, and reduced global ac4C levels. Quetiapine treatment potently suppressed HNSCC cell proliferation and migration, while promoting apoptosis. Mechanistically, quetiapine-mediated NAT10 inhibition downregulated key OXPHOS components and substantially decreased cellular OCR, indicating impaired mitochondrial respiration.</p><p><strong>Conclusions: </strong>NAT10 functions as a critical oncoprotein in HNSCC, potentially by enhancing OXPHOS-driven energy metabolism. The repurposed drug quetiapine suppresses tumor growth by targeting the NAT10/ac4C axis and disrupting mitochondrial respiratory function, positioning it as a promising therapeutic agent for HNSCC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 3","pages":"175"},"PeriodicalIF":1.7,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of competing-risk nomograms and identification of optimal candidates for aggressive therapy in gastric cancer with peritoneal metastasis: a population-based study.","authors":"Zhifan Zhang, Chenchen Lu, Wen Wang, Jing Yang, Zaixiang Tan","doi":"10.21037/tcr-2025-1-2692","DOIUrl":"https://doi.org/10.21037/tcr-2025-1-2692","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The optimal treatment strategies for gastric cancer with peritoneal metastasis (GCPM) are extensively debated, especially regarding the appropriateness of aggressive local treatments. This study aimed to construct robust competing-risk nomograms for prognostic prediction and to establish a novel risk-stratification system to facilitate individualized therapeutic decision-making.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Patients diagnosed with GCPM between 2010 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided into training and validation cohorts at a 7:3 ratio. Propensity score matching (PSM) was applied to evaluate the survival impact of different treatment strategies. Independent prognostic factors in the training cohort were selected using a combination of least absolute shrinkage and selection operator (LASSO) regression and stepwise Akaike information criterion (AIC), and these variables were subsequently used to construct Cox [for overall survival (OS)] and Fine-Gray [for cancer-specific survival (CSS)] nomograms. Model discrimination, calibration, predictive accuracy, and clinical utility were assessed using the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Risk stratification was further performed based on the nomogram-derived scores, and treatment benefits were analyzed across different risk groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 4,280 patients were included, comprising 2,996 in the training cohort and 1,284 in the validation cohort. PSM analysis demonstrated that, among unstratified patients, aggressive therapy significantly improved survival compared with chemotherapy-based treatment (P&lt;0.001). Twelve independent prognostic factors, including treatment strategy, tumor grade, and metastatic burden, were identified for the construction of nomograms. The OS and CSS nomograms demonstrated favorable discrimination [C-index: 0.68-0.71; 2-year area under the curve (AUC): 0.792; 95% confidence interval (CI): 0.769-0.815] and calibration in both cohorts, while DCA suggested a potential for greater clinical net benefit than the American Joint Committee on Cancer (AJCC) staging system across a range of threshold probabilities. Risk stratification utilizing nomogram scores effectively distinguished subgroups with different prognostic levels. Treatment-benefit analyses revealed that aggressive therapy was associated with significantly reduced the risk of death in the low-risk group [hazard ratio (HR) =0.6, P&lt;0.001], whereas it was associated with increased mortality risk in the high-risk group (characterized by advanced age and extensive tumor burden; HR &gt;1, P&lt;0.001).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study developed and validated competing-risk nomograms for GCPM patients and proposed a new risk-stratification system. This system supports the concept of risk-","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 3","pages":"161"},"PeriodicalIF":1.7,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic alternative splicing signatures in esophageal cancer reveal SF3A3 as a key oncogenic splicing factor.","authors":"Junxian Mo, Yuntao Zou, Jiangsheng Zhang, Huikai Miao, Dongni Chen","doi":"10.21037/tcr-2025-1-2662","DOIUrl":"https://doi.org/10.21037/tcr-2025-1-2662","url":null,"abstract":"<p><strong>Background: </strong>Esophageal cancer (ESCA) is a highly lethal malignancy with limited therapeutic options, largely due to late-stage diagnosis and molecular complexity. Dysregulated alternative splicing (AS) contributes to ESCA progression, but its prognostic and mechanistic roles remain poorly characterized. The aim of this study is to investigate the role of AS in ESCA progression and to elucidate its potential as a prognostic factor.</p><p><strong>Methods: </strong>The percent spliced in (PSI) values for seven subtypes of AS events, RNA-seq and clinical information of ESCA cohorts were retrieved from The Cancer Genome Atlas (TCGA) database. Survival-related AS events were identified through Cox regression analysis. The AS events were integrated to formulate the prognostic signature both for overall survival (OS) and progression-free interval (PFI). ESCA patients were categorized into high- or low-risk groups using the median risk score of the signature. Kaplan-Meier analysis, receiver operating characteristic (ROC) analyses, and Cox regression were performed to evaluate the prognostic efficacy of this signature. Cell proliferation was measured with Cell Counting Kit-8 (CCK8) and colony formation. Tumor xenograft experiment was performed to evaluate the tumor growth of ESCA cells <i>in vivo</i>.</p><p><strong>Results: </strong>We identified 27,611 AS events in 162 ESCA patients from TCGA, with exon skipping, alternate promoter, and alternate terminator as the most common types. A prognostic signature integrating all seven AS types accurately predicted OS and PFI in ESCA. Patients with a high-risk score demonstrated a poor prognosis. The splicing factor SF3A3 was found to promote esophageal squamous cell carcinoma (ESCC) cell proliferation and tumor growth by regulating the AS of LGALS9.</p><p><strong>Conclusions: </strong>This study identified survival-associated AS signatures, potentially improving the prediction of survival outcomes in ESCA patients. Moreover, the splicing factor SF3A3 was shown to promote tumor progression by regulating AS of LGALS9, suggesting it as a promising therapeutic target.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 3","pages":"145"},"PeriodicalIF":1.7,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: LncRNA CASC9 regulates cell proliferation, apoptosis and cell cycle via sponging miR-145-5p in colon cancer cells.","authors":"","doi":"10.21037/tcr-20262-1","DOIUrl":"https://doi.org/10.21037/tcr-20262-1","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.21037/tcr.2019.10.33.].</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 3","pages":"224"},"PeriodicalIF":1.7,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>GPR176</i> represses mitophagy to promote the progression of osteosarcoma by facilitating mTORC1 activity via PI3K-AKT pathway.","authors":"Jiyong Jiang, Bowen Zheng, Jing Wang, Yi Fang, Lianbo Yang, Jinghang Lv, Haidong Liang","doi":"10.21037/tcr-2025-2146","DOIUrl":"https://doi.org/10.21037/tcr-2025-2146","url":null,"abstract":"<p><strong>Background: </strong>Osteosarcoma (OS) is a common primary malignant tumor of the bone. It is reported that abnormal <i>GPR176</i> expression contributes to the occurrence and subsequent progression of tumors. However, the role of <i>GPR176</i> in OS has not been elucidated. Thus, the aim of this study was to evaluate the role of <i>GPR176</i> in the progression of OS.</p><p><strong>Methods: </strong>The expression level and prognosis of <i>GPR176</i> were explored based on Gene Expression Omnibus (GEO), TARGET and Genotype-Tissue Expression (GTEx) databases, as well as the involved pathways. Effects of <i>GPR176</i> on the proliferation, migration, invasion, and apoptosis of U2OS cells, as well as in a mouse tumor xenograft model. Multiple parameters were employed to explore the role of <i>GPR176</i> in mitophagy, including mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and mitophagy-related proteins. The protein levels of downstream substrates of mTORC1 were analyzed by Western blot.</p><p><strong>Results: </strong>The expression level of <i>GPR176</i> was obviously elevated in OS, and increased <i>GPR176</i> expression associated with poor prognosis in patients with OS. Gene Set Enrichment Analysis (GSEA) showed that <i>GPR176</i> is mainly involved in the oxidative phosphorylation, retinol metabolism, and ErbB signaling pathways. <i>GPR176</i> knockdown suppressed the proliferation, migration, and invasion of U2OS cells and enhanced their apoptosis. <i>GPR176</i> downregulation also induced mitophagy in U2OS cells, as evidenced by an increase in ROS levels; a decrease in MMP, adenosine triphosphate (ATP), and mitochondrial DNA (mtDNA); and concomitant changes in mitophagy-related proteins. <i>GPR176</i> knockdown suppresses mTORC1 activity in U2OS cells. Moreover, <i>GPR176</i> knockdown represses the growth of tumor xenografts in vivo while promoting mitophagy. The levels of phosphorylated-mechanistic target of rapamycin complex 1 (p-mTORC1)/mTORC1, p-v-akt murine thymoma viral oncogene homolog 1 (AKT)/AKT, and p-phosphatidylinositol-3 kinase (PI3K)/PI3K were significantly downregulated following <i>GPR176</i> knockdown.</p><p><strong>Conclusions: </strong><i>GPR176</i> is upregulated in OS and is associated with a poor prognosis. <i>GPR176</i> suppresses mitophagy to promote OS progression by facilitating mTORC1 activity via the PI3K-AKT pathway.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 3","pages":"193"},"PeriodicalIF":1.7,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}