Cancer Cell International最新文献

{"title":"STIM1 signaling modulates invasive phenotypic plasticity by regulating calpain-dependent cleavage of integrin-β4 in nasopharyngeal carcinoma cells.","authors":"Weiming Deng, Wenlin Huang, Yujuan Huang, Lihong Huang, Linsong Ye, Fei Liu, Min Li, Jingjin Weng, Qian He, Jinyan Zhang, Shenhong Qu, Jiazhang Wei","doi":"10.1186/s12935-025-03890-z","DOIUrl":"10.1186/s12935-025-03890-z","url":null,"abstract":"<p><strong>Background: </strong>Stromal interaction molecule 1 (STIM1)-mediated Ca²⁺ signaling modulates the malignant features of nasopharyngeal carcinoma (NPC), a unique Epstein-Barr virus (EBV)-associated human malignancy. Integrin-β4 is involved in EBV-promoted motility in NPC cells. However, the underlying mechanism through which STIM1 signaling manipulates the invasive characteristics of NPC cells and the implication of integrin-β4 remains elusive. The present study aimed to characterize the role of integrin-β4 in the phenotypic plasticity for the epithelial-mesenchymal and mesenchymal-epithelial transitions (EMT and MET), and determine whether STIM1 signaling enhances invasive potential by modulating integrin-β4 cleavage in NPC cells.</p><p><strong>Methods: </strong>Western blotting of epithelial and mesenchymal markers, cell migration and colony formation assays were performed to evaluate the EGF-stimulated EMT and laminin-induced MET in vitro. A zebrafish xenograft model was employed to elucidate the proliferation of transplanted NPC cell spheroids in vivo. A tail vein injection-lung metastasis mouse model was utilized to determine the capacity for distant metastatic colonization of NPC cells. Immunohistochemical analysis was conducted to detect the expression level of integrin-β4 in NPC tissues.</p><p><strong>Results: </strong>Integrin-β4 was required for the bi-directional epithelial-mesenchymal transition in NPC cells. Silencing of integrin-β4 inhibited cell migration and clonogenicity in vitro, reduced clonal expansion of tumor cell clusters in zebrafishes, and eliminated distant metastatic colonization in mice. STIM1 Ca²⁺ signaling modulated the redistribution of integrin-β4 in migrating NPC cells. Mechanistically, STIM1-mediated Ca²⁺ influx enhanced aggregation of integrin-β4 at the cell membranes by promoting the calpain-dependent cleavage of integrin-β4. Clinically, we confirmed that integrin-β4 was highly expressed in primary tumors and cervical lymph node metastases.</p><p><strong>Conclusion: </strong>STIM1 signaling promotes invasiveness by enabling accelerated subcellular integrin-β4 redistribution, which is essential for maintaining the invasive plasticity of NPC cells.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"253"},"PeriodicalIF":5.3,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Molecular and phenotypic characterization of 5-FU resistant colorectal cancer cells: toward enrichment of cancer stem cells.","authors":"Amirhesam Babajani, Saeed Rahmani, Mohammad Jamal Asadi, Elmira Gheytanchi, Glavizh Adibhesami, Faezeh Vakhshiteh, Zahra Madjd","doi":"10.1186/s12935-025-03891-y","DOIUrl":"10.1186/s12935-025-03891-y","url":null,"abstract":"","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"252"},"PeriodicalIF":5.3,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIF-1α and HIF-2α: synergistic regulation of glioblastoma malignant progression during hypoxia and apparent chemosensitization in response to hyperbaric oxygen.","authors":"Pan Wang, Sheng Gong, Bin Liao, Jie Liu, Lu Zhao, Nan Wu","doi":"10.1186/s12935-025-03823-w","DOIUrl":"10.1186/s12935-025-03823-w","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM), the most malignant type of brain tumour, is regulated mainly by a hypoxic microenvironment. Previous studies have focused mainly on the effects of hypoxia inducible factor-1α (HIF-1α) or hypoxia inducible factor-2α (HIF-2α) alone on GBM, and the results have shown that each factor regulates the malignant progression of GBM, but the single knockout of either gene does not markedly influence this regulation. This study was performed to determine whether HIF-1α and HIF-2α synergistically regulate the malignant progression of GBM. Therefore, HIF-1α and HIF-2α were knocked out in GBM cells. Compared with single HIF-1α- or HIF-2α-knockout and control cells, cells with simultaneous knockout of HIF-1α- and HIF-2α presented significantly greater changes, including differential gene expression and changes in biological process, cellular component, and molecular function GO terms, and enriched KEGG pathways. In addition, dual-knockout cells were induced to transition to G₂/M + S phase, exhibiting the greatest growth rate but the lowest degree of stemness and invasion; after temozolomide (TMZ) treatment, the dual-knockout cells exhibited the greatest rate of apoptosis and lactate dehydrogenase (LDH) release and the lowest growth rate and tumour size and weight, resulting in the longest survival time. Hyperbaric oxygen (HBO) is an effective method for alleviating GBM-related hypoxia; we investigated phenotypic changes in HBO-treated cells and observed increased growth rates but decreased HIF-1α and HIF-2α expression and a decreased degree of stemness. After TMZ exposure, HBO-treated cells presented increased apoptosis rates and LDH release and decreased tumour size and weight, resulting in increased survival. These results suggest that HIF-1α and HIF-2α together exhibit synergistic regulation and play major regulatory roles in GBM. Simultaneous targeting of both HIF-1α and HIF-2α with TMZ is an important method for treating GBM patients and improving patients' prognosis. Therefore, HBO can be used in GBM treatment because of its ability to sensitize cells to chemotherapy via the significant inhibition of both HIF-1α and HIF-2α expression.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"251"},"PeriodicalIF":5.3,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12232062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MYO1B promotes radioresistance in head and neck squamous cell carcinoma by regulating tumor stemness and DNA damage repair via the PI3K/AKT pathway.","authors":"Yanan Li, Jiahao Liu, Zhen Wang, Yilei Zhang, Baiying Liu, Ling Chu","doi":"10.1186/s12935-025-03863-2","DOIUrl":"10.1186/s12935-025-03863-2","url":null,"abstract":"<p><p>Head and Neck Squamous Cell Carcinoma is a prevalent malignancy characterized by high recurrence rates. While surgery remains the primary treatment, postoperative radiotherapy is essential for preventing tumor recurrence. However, the mechanisms driving radiotherapy resistance in HNSC remain largely unknown. With a multi-layered approach encompassing bioinformatics analysis, clinical tissue sample validation, in vitro and in vivo experiments, we discovered that MYO1B played a critical role in radiotherapy resistance of HNSC. Our findings underscored that MYO1B was significantly overexpressed in HNSC tissues and was associated with poor prognosis, particularly in patients undergoing radiotherapy. Functional investigations revealed that knockdown of MYO1B reduced the expression of stemness markers (SOX2, OCT4), decreased EMT-related protein levels, inhibited the phosphorylation of the key DNA damage repair protein ATM and increased sensitivity to radiotherapy. Mechanistically, knockdown of MYO1B inhibited the PI3K/AKT signaling pathway to reduce the expression of stemness-and DNA damage repair-related genes, and the use of an AKT activator reversed the observed reductions in tumor stemness and radiotherapy resistance. In vivo, MYO1B knockdown led to reduced tumor growth and enhanced radiotherapy sensitivity in a xenograft model. Clinical sample validation discovered that MYO1B was associated with disease-free survival, potentially due to higher tumor stemness and lower CD8 + cell infiltration. In summary, our study provides novel insights into the role of MYO1B in HNSC and highlights its potential as a therapeutic target for overcoming radiotherapy resistance.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"248"},"PeriodicalIF":5.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Petiveria alliacea and Caesalpinia spinosa extracts reduce the generation of cancer-associated fibroblasts in a 3D platform representative of the tumor microenvironment.","authors":"María Camila Jimenez, Paola Lasso, Susana Fiorentino, Alfonso Barreto","doi":"10.1186/s12935-025-03860-5","DOIUrl":"10.1186/s12935-025-03860-5","url":null,"abstract":"<p><strong>Background: </strong>The tumor microenvironment (TME) is a complex network of cellular and acellular participants, each of which contributes to ensuring tumor growth. Cancer-associated fibroblasts (CAFs) represent a key TME population that actively participates in stromal remodeling and metabolic coupling with tumors, significantly favoring both the process of carcinogenesis and the establishment of metastasis. Therefore, developing therapies that target CAFs constitute valuable therapeutic alternatives. However, efficiently modeling the generation of CAFs in the tumor microenvironment is challenging.</p><p><strong>Methods: </strong>We constructed a 3D structure of the tumor microenvironment (TME), which we refer to as \"TME spheroids\". These spheroids are composed of 4T1 murine breast cancer cells and 3T3 murine fibroblasts, allowing us to mimic the development of a cancer-associated fibroblast (CAF) phenotype. This novel 3D model serves as a platform for evaluating the impact of two natural extracts on TME interactions and their ability to impede tumor progression.</p><p><strong>Results: </strong>Using the TME-spheroid model, we tested the effects of two extracts on CAF generation: Anamu-SC obtained from Petiveria alliacea and P2Et from Caesalpinia spinosa. Both extracts disrupted the interaction between tumor cells and fibroblasts, reducing the ability of CAFs to support tumor growth and spread.</p><p><strong>Conclusions: </strong>We found that the two extracts interfere with circuits that drive tumor-fibroblast crosstalk, attenuating the phenotype and functional activities associated with CAFs in this TME model.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"243"},"PeriodicalIF":5.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory mechanisms and clinical implications of PIWI-interacting RNAs (piRNAs) in major digestive tract cancers.","authors":"Penghui Li, Yuan Xue, Xinyu Gu","doi":"10.1186/s12935-025-03889-6","DOIUrl":"10.1186/s12935-025-03889-6","url":null,"abstract":"<p><p>Cancers of the digestive tract, including those affecting the esophagus, stomach, liver, pancreas, and colorectum, impose a substantial global health burden due to their high morbidity and mortality rates. Despite advancements in diagnostic and treatment modalities, the molecular mechanisms underpinning the initiation and progression of digestive tract cancers remain incompletely understood. Recent progress in high-throughput sequencing technology has uncovered the crucial role of small non-coding RNAs (ncRNAs) in regulating gene expression and maintaining genomic stability across various cancers, including those affecting the digestive tract. P-element-induced wimpy testis (PIWI)-integrating RNAs (piRNAs), a subset of small ncRNAs, emerge as pivotal regulators in preserving genome integrity by suppressing transposable elements in germline cells. Growing evidence implicates piRNAs in the development and advancement of digestive tract cancers. Notably, piRNAs exhibit complex and multifaceted roles in these tumors, functioning as both tumor suppressors and oncogenes. They exert their effects through diverse mechanisms, including post-transcriptional gene silencing, epigenetic modifications, and modulation of signaling pathways involved in tumorigenesis, such as the Wnt/β-catenin, PI3K/Akt, and MAPK pathways. Dysregulation of piRNAs disrupts key cellular processes, including cell cycle regulation, apoptosis, epithelial-mesenchymal transition, and metastasis, across various digestive tract cancers. Moreover, distinct expression profiles of specific piRNAs correlate with diverse clinical features and outcomes in individuals afflicted with digestive tract cancers, highlighting their potential as diagnostic and prognostic biomarkers in this context. Furthermore, therapeutic interventions targeting dysregulated piRNAs or their downstream effectors hold promise as novel avenues for precision medicine approaches in managing digestive tract cancers. In this review, we summarize the current understanding of piRNAs in digestive tract cancers, focusing on their dual roles as both tumor suppressors and oncogenes. We further delve into the intricate molecular mechanisms by which piRNAs modulate crucial cellular processes implicated in tumorigenesis. Additionally, we explore the potential of piRNAs as valuable diagnostic, prognostic, and therapeutic biomarkers in the landscape of digestive tract cancers. By elucidating the complex interplay between piRNAs and digestive tract cancers, this review aims to offer insights into novel therapeutic strategies centered around targeting piRNAs for precision medicine approaches in the management of these malignancies.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"244"},"PeriodicalIF":5.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination of astragalus polysaccharide with Diosbulbin B exerts an enhanced antitumor effect in BRAF^mut papillary thyroid cancer with decreased liver toxicity.","authors":"Shuai Xu, Qi Liang, Hang Li, Hai Zhou, Zhenyuan Xu, Yanjun Yan, Yue Zhang, Renqun Ye, Xujun You","doi":"10.1186/s12935-025-03853-4","DOIUrl":"10.1186/s12935-025-03853-4","url":null,"abstract":"<p><strong>Background: </strong>Diosbulbin B (DB) is a traditional Chinese medicine used for thyroid cancer treatment, but always brings severe liver injury. In the current study, we investigated the role of astragalus polysaccharide (APS) in DB-induced hepatotoxicity and their anti-tumor effect on BRAF^mut papillary thyroid cancer (PTC), and disclosed the underlying mechanisms.</p><p><strong>Methods: </strong>Two BRAF^mut PTC IHH-4 and GLAG-66 cell lines were applied for the in vitro assays. CCK-8, flow cytometry, transwell chambers, enzyme-linked immunosorbent assay (ELISA) and transmission electron microscopy (TEM) were performed for cell growth, apoptosis, migration/invasion, malondialdehyde (MDA)/glutathione (GSH) content and mitochondria damage detection. Human normal liver epithelial cell line THLE-2 was used to assess the liver toxicity, together with the animal experiment.</p><p><strong>Results: </strong>The IC50 of APS and DB in IHH-4 cells were 153.9 µg/mL and 41.2 µM, respectively, while they were 728.0 µg/mL and 22.74 µM in GLAG-66 cells. Combination of APS and DB enhanced the anti-cancer role of DB with increased cell apoptosis and LDH release, and weakened cell growth, migration and invasion capacities. Interestingly, the combination of these two drugs significantly alleviated the liver injury induced by DB. In mechanism, we found that APS combined with DB treatment triggered the increase of MDA level while decreased GSH level, and deteriorated mitochondria damage. Inhibition of ferroptosis impaired the anti-PTC role of APS combined with DB with no influencing on liver injury both in vivo and in vitro.</p><p><strong>Conclusions: </strong>In conclusion, our study shows the combined therapy strategy of APS and DB regimen achieves better anti-cancer response through increasing MDA level while decreasing GSH level. Importantly, the combined therapy of APS and DB significantly decreased the liver toxicity induced by DB. These findings suggest that APS combined DB is a potential therapeutic strategy for BRAF^mut PTC with high efficacy and low liver toxicity.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"245"},"PeriodicalIF":5.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P4HA2 promotes the progression of papillary thyroid cancer by enhancing degradation of IκBα to activate NF-κB signaling pathway.","authors":"Ruowen Li, Mingjian Zhao, Min Sun, Yongkang Wu, Chengxu Miao, Liu Fangyu, Mengting Wu, Xiaojia Shi, Jinghui Lu, Xuetian Yue","doi":"10.1186/s12935-025-03871-2","DOIUrl":"10.1186/s12935-025-03871-2","url":null,"abstract":"<p><p>Papillary thyroid cancer (PTC) is the most common malignancy of the endocrine system. Collagen prolyl 4-hydroxylase alpha subunit 2 (P4HA2) is a key enzyme involved in collagen metabolism. However, the expression and function of P4HA2 in PTC progression have not been well studied. Our previous proteomic data showed that the differential proteins in human PTC were significantly enriched in metabolic signaling pathways, with P4HA2 being the most up-regulated protein. Here, we found that P4HA2 promotes the proliferation and migration of PTC. The expression of P4HA2 is elevated and its elevation is associated with poor prognosis in human PTC specimens. Functionally, P4HA2 promotes the proliferative and migratory abilities of BHP10-3 and TPC-1 cells. Further studies showed that overexpression of P4HA2 significantly activates the NF-κB signaling pathway. Mechanistically, P4HA2 promotes the ubiquitination and degradation of inhibitor kappa B-alpha (IκBα) by directly binding, leading to activation of NF-κB signaling pathway. Furthermore, BAY 11-7082, an inhibitor of the NF-κB signalling pathway, reversed the promotion of PTC proliferation and metastasis by P4HA2 both in vivo and in vitro. In conclusion, P4HA2 activates the NF-κB signaling pathway by promoting proteasome-dependent degradation of IκBα, which in turn contributes to the proliferation and migration of PTC. Therefore, P4HA2 could be used as a potential therapeutic target for the treatment of PTC patients.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"249"},"PeriodicalIF":5.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bio-engineered microRNA-7 effectively interferes with the Akt3/p53 axis to suppress human non-small cell lung cancer.","authors":"Qian Huang, Xiaohua Chu, Chaofei Yang, Ying Huai, Chenyang He, Xingcong Ma, Jiawei Pei, Junhong Gao, Zhiyong Liu, Shanfeng Jiang, Airong Qian, Ye Tian","doi":"10.1186/s12935-025-03856-1","DOIUrl":"10.1186/s12935-025-03856-1","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) remains the leading cause of cancer deaths worldwide. Unfortunately, effective treatment is still lacking. The p53 tumor-suppressor protein is a critical mediator of cellular growth arrest and apoptosis, and is closely related to NSCLC. Importantly, microRNAs (miRs) have been shown to influence tumor progression by targeting p53. Therefore, we screened p53-associated miRs that were differentially expressed in NSCLC and benign tissues by bioinformatic analysis. Among them miR-7 was implicated in multiple tumorigenesis related pathways. Then the novel hybrid tRNA scaffold was used to produce bio-engineered miR-7 and its inhibition to NSCLC as well as the interaction with p53 was investigated. We found that overexpression of miR-7 in NSCLC significantly inhibited the proliferation, migration, invasion, and induced apoptosis of NSCLC cells. And in vivo study exhibited dramatic inhibition of tumor growth by bio-engineered miR-7 in orthotopic NSCLC xenograft tumor mouse model. In addition, we identified Akt3 as a novel target of miR-7, the suppression of tumor growth and sensitization of chemotherapy drugs by miR-7 was related to the repression of Akt which activated MDM2-mediated ubiquitination and degradation of p53. Our results reported for the first time that miR-7 could target Akt3 and interact with genes in the p53 pathway to suppress the development of NSCLC, which also implied the therapeutic potential of bio-engineered miR-7 for NSCLC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"250"},"PeriodicalIF":5.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 molecular subtypes based on pseudouridine modification in hepatocellular carcinoma.","authors":"Weifeng Xu, Caiyun Nie, Zhen Liu, Yingjun Liu, Penghui Yu, Huifang Lv, Beibei Chen, Jianzheng Wang, Saiqi Wang, Jing Zhao, Yunduan He, Shegan Gao, Xiaobing Chen","doi":"10.1186/s12935-025-03844-5","DOIUrl":"10.1186/s12935-025-03844-5","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a highly aggressive disease with a dismal prognosis. The recently described role of RNA pseudouridine modification in regulating anti-tumor immunity has attracted interest, but the understanding of its impact on hepatocellular carcinoma progression and immune evasion is limited. Here, we reveal that HCC could be categorized into pseudouridine-low, and -high subtypes with distinct clinicopathologic features, prognostic and tumor microenvironment. In general, the pseudouridine-high subtype presents a dismal prognosis with the immunosuppressive microenvironment. Inversely, the pseudouridine-low subtype was associated with favorable clinical outcomes with the immunoreactive microenvironment. Moreover, we develop and validate a pseudouridine-related prognostic model, which shows strong power for prognosis assessment. More importantly, we identified RPUSD3 as a critical pseudouridine modification gene. RPUSD3 knockdown inhibits hepatocellular carcinoma growth in vivo, increasing CD8 T cell infiltration. In conclusion, we established a novel HCC classification based on the RNA pseudouridine modification subtype. This classification had significant outcomes for estimating the prognosis, as well as the tumor microenvironment.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"247"},"PeriodicalIF":5.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12225032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}