Cancer Cell International最新文献

{"title":"Regulation of microtubule nucleation in glioblastoma cells by ARF GTPase-activating proteins GIT1 and GIT2 and protein kinase C.","authors":"Vadym Sulimenko, Eduarda Dráberová, Vladimíra Sládková, Tetyana Sulimenko, Věra Vosecká, Omar Skalli, Pavel Dráber","doi":"10.1186/s12935-025-03740-y","DOIUrl":"10.1186/s12935-025-03740-y","url":null,"abstract":"<p><strong>Background: </strong>G protein-coupled receptor kinase-interacting proteins (GITs) function as GTPase-activating proteins (GAPs) for small GTPases of the ADP-ribosylation factor (Arf) family. While GIT proteins (GIT1 and GIT2) regulate both cell migration and microtubule organization, their corresponding regulatory mechanisms in glioblastoma cells remain largely unknown. To further investigate their role in microtubule modulation, we examined the function of GITs in microtubule nucleation and the involvement of protein kinase C (PKC) in this process.</p><p><strong>Methods: </strong>Glioblastoma cell lines with depleted GIT protein levels were generated using shRNA lentiviral vectors. The cellular localization of GITs was visualized by immunofluorescence microscopy, microtubule nucleation was analyzed using time-lapse imaging, and cell migration was assessed through a wound healing assay. Phosphomimetic and non-phosphorylatable variants of GIT2 were prepared by site-directed mutagenesis. Immunoprecipitation, pull-down experiments, and kinase assays in the presence of PKC inhibitors were used to study protein interactions.</p><p><strong>Results: </strong>Both GIT1 and GIT2 associate with proteins of the γ-tubulin ring complexes (γTuRCs), the primary microtubule nucleators, and localize to centrosomes. Depletion of GIT2 enhances centrosomal microtubule nucleation and has a more pronounced, yet opposite, effect on this process compared to GIT1. In contrast, the depletion of both GIT1 and GIT2 similarly affects cell migration. The N-terminal ArfGAP domain of GIT2 associates with centrosomes, regulates microtubule nucleation, and is phosphorylated by PKC, which modulates this process. We identified serine 46 (S46) on the ArfGAP domain as a PKC phosphorylation site and demonstrated that phosphorylation of GIT2 at S46 promotes microtubule nucleation.</p><p><strong>Conclusions: </strong>We propose that GIT2 phosphorylation provides a novel regulatory mechanism for microtubule nucleation in glioblastoma cells, contributing to their invasive properties.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"125"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11963297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771158","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":"Non-coding RNAs, a double-edged sword in breast cancer prognosis.","authors":"Maryam Solaimani, Sahar Hosseinzadeh, Mozhgan Abasi","doi":"10.1186/s12935-025-03679-0","DOIUrl":"10.1186/s12935-025-03679-0","url":null,"abstract":"<p><p>Cancer is a rising issue worldwide, and numerous studies have focused on understanding the underlying reasons for its occurrence and finding proper ways to defeat it. By applying technological advances, researchers are continuously uncovering and updating treatments in cancer therapy. Their vast functions in the regulation of cell growth and proliferation and their significant role in the progression of diseases, including cancer. This review provides a comprehensive analysis of ncRNAs in breast cancer, focusing on long non-coding RNAs such as HOTAIR, MALAT1, and NEAT1, as well as microRNAs such as miR-21, miR-221/222, and miR-155. These ncRNAs are pivotal in regulating cell proliferation, metastasis, drug resistance, and apoptosis. Additionally, we discuss experimental approaches that are useful for studying them and highlight the advantages and challenges of each method. We then explain the results of these clinical trials and offer insights for future studies by discussing major existing gaps. On the basis of an extensive number of studies, this review provides valuable insights into the potential of ncRNAs in cancer therapy. Key findings show that even though the functions of ncRNAs are vast and undeniable in cancer, there are still complications associated with their therapeutic use. Moreover, there is an absence of sufficient experiments regarding their application in mouse models, which is an area to work on. By emphasizing the crucial role of ncRNAs, this review underscores the need for innovative approaches and further studies to explore their potential in cancer therapy.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"123"},"PeriodicalIF":5.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762975","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":"LncRNA SPINT1-AS1 enhances the Warburg effect and promotes the progression of osteosarcoma via the miR-135b-5p/PGAM1 axis.","authors":"Jinyou Wang, Ning Zhang, Yan Wang, Fanghong Chen, Lei Wang, Kailun Wang, Xiao Yao, Xiaohui Pan","doi":"10.1186/s12935-025-03761-7","DOIUrl":"10.1186/s12935-025-03761-7","url":null,"abstract":"<p><p>Osteosarcoma (OS) is a malignant bone tumor that originates from interstitial tissues and affects the health of children and adolescents. Long noncoding RNAs (lncRNAs) are an intriguing category of widely distributed endogenous RNAs involved in OS progression, many of which remain functionally uncharacterized. Herein, we observed an increased expression of lncRNA SPINT1-AS1 in OS tissues and cell lines. Further analysis confirmed that SPINT1-AS1 promotes the proliferation and metastasis of OS cells. Moreover, miR-135b-5p was identified as a downstream target of SPINT1-AS1. Through bioinformatics analysis, PGAM1 mRNA was validated as a target of miR-135b-5p via RIP and luciferase reporter assays. SPINT1-AS1 could enhance OS cell proliferation and metastasis by promoting aerobic glycolysis, acting as a ceRNA by binding to miR-135b-5p, thereby increasing PGAM1 expression. Taken together, these results indicate that SPINT1-AS1 functions as a tumor promoter and regulates OS cell progression through the miR-135b-5p/PGAM1 axis.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"124"},"PeriodicalIF":5.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11963676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762974","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":"The m6A reader IGF2BP2 promotes pancreatic cancer progression through the m6A-SLC1A5-mTORC1 axis.","authors":"Xi Pu, Yuting Wu, Weiguo Long, Xinyu Sun, Xiao Yuan, Deqiang Wang, Xu Wang, Min Xu","doi":"10.1186/s12935-025-03736-8","DOIUrl":"10.1186/s12935-025-03736-8","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic cancer is a highly malignant digestive tumor. Glutamine metabolism is one of the important sources of tumors. N6-methyladenosine (m6A) modification plays a key role in regulating tumor metabolism and holds promise as a therapeutic target in various cancers, including pancreatic cancer. Disrupting m6A regulation of glutamine metabolism could impair tumor growth, offering potential new therapeutic strategies. However, the functional role of m6A modifications in pancreatic cancer, especially in glutamine metabolism, remains poorly understood.</p><p><strong>Methods: </strong>The Cancer Genome Atlas (TCGA) dataset and GEPIA bioinformatics tool were used to identify the relationship between m6A related proteins and the glutamine metabolism-associated genes, respectively. The biological effects of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) were investigated using in vitro and in vivo models. Methylated RNA immunoprecipitation sequencing (MeRIP-seq), MeRIP-PCR and RNA immunoprecipitation (RIP) were used to identify solute carrier family 1 member 5 (SLC1A5) as a direct target of IGF2BP2.</p><p><strong>Results: </strong>We found that IGF2BP2 expression and SLC1A5 were significantly correlated and both highly expressed in pancreatic cancer could predict poor prognosis in patients with pancreatic cancer. Functionally, silencing IGF2BP2 suppressed tumor growth and also inhibited glutamine uptake by tumor cells. Mechanistically, IGF2BP2 induced the m6A-SLC1A5-mTORC1 axis, facilitating the uptake of glutamine by pancreatic cancer cells and accelerate the progress of pancreatic cancer. Furthermore, silencing IGF2BP2 can enhance the sensitivity of pancreatic cancer to radiotherapy and chemotherapy.</p><p><strong>Conclusion: </strong>Our findings suggest that IGF2BP2 promotes pancreatic cancer by activating the m6A-SLC1A5 -mTORC1 axis. Targeting the m6A machinery, particularly IGF2BP2, offers a novel therapeutic avenue for pancreatic cancer treatment. By disrupting the regulation of glutamine metabolism, we provide new insights into how m6A-based therapies could enhance the efficacy of current treatments and offer hope for improving patient outcomes in this difficult-to-treat cancer.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"122"},"PeriodicalIF":5.3,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742519","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":"CircITGA7 overexpression suppresses HCC progression via miR-330/BCL11B axis regulation.","authors":"Zhijie Li, Hui Ren, Shuaishuai Tan, Bing Su, Yuchen Wang, Wenwen Ren, Boyang Zhang, Can Song, Rulong Du, Yuchun Gu, Lida Wu, Hongyu Li","doi":"10.1186/s12935-025-03714-0","DOIUrl":"https://doi.org/10.1186/s12935-025-03714-0","url":null,"abstract":"<p><p>As a kind of prevalent malignancy globally, hepatocellular carcinoma (HCC) is characterized by significant morbidity and mortality due to the difficulties in early diagnosis and limited treatment options. Circular RNAs (circRNAs) are a type of circular single-stranded RNA molecule formed by the back-splicing of the 5' end and the 3' end of linear RNA, possessing multiple biological functions. In recent years, numerous reports have demonstrated that circRNAs are potential biomarkers and therapeutic targets for HCC. In this study, we found that circITGA7 is significantly downregulated in HCC tissue compared to adjacent non-tumor tissue. Functional experiments such as CCK8, EdU, colony formation and wound healing assays proved that overexpression of circITGA7 can effectively inhibit the proliferation, migration and invasion of HCC cells. Further research found that circITGA7 can inhibit miR-330 to release BCL11B expression, thereby promoting P53 expression, blocking the cell cycle and promoting apoptosis in HCC cells. In addition, circITGA7 can impede the proliferation of HCC cells in vivo. Therefore, circITGA7 is a potential biomarker for the diagnosis of HCC development and a potential target for the treatment of HCC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"121"},"PeriodicalIF":5.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742518","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":"Integrated single-cell and bulk transcriptomic analysis identifies a novel macrophage subtype associated with poor prognosis in breast cancer.","authors":"Qing Wang, Yushuai Yu, Liqiong Ruan, Mingyao Huang, Wei Chen, Xiaomei Sun, Jun Liu, Zirong Jiang","doi":"10.1186/s12935-025-03750-w","DOIUrl":"10.1186/s12935-025-03750-w","url":null,"abstract":"<p><strong>Background: </strong>Tumor-associated macrophages (TAMs) are pivotal components of the breast cancer (BC) tumor microenvironment (TME), significantly influencing tumor progression and response to therapy. However, the heterogeneity and specific roles of TAM subpopulations in BC remain inadequately understood.</p><p><strong>Methods: </strong>We performed an integrated analysis of single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (RNA-seq) data from BC patients to comprehensively characterize TAM heterogeneity. Utilizing the MetaTiME computational framework and consensus clustering, we identified distinct TAM subtypes and assessed their associations with clinical outcomes and treatment responses. A machine learning-based predictive model was developed to evaluate the prognostic significance of TAM-related gene expression profiles.</p><p><strong>Results: </strong>Our analysis revealed three distinct TAM subgroups. Notably, we identified a novel macrophage subtype, M_Macrophage-SPP1-C1Q, characterized by high expression of SPP1 and C1QA, representing an intermediate differentiation state with unique proliferative and oncogenic properties. High infiltration of M_Macrophage-SPP1-C1Q was significantly associated with poor overall survival (OS) and chemotherapy resistance in BC patients. We developed a Random Forest (RF)-based predictive model, Macro.RF, which accurately stratified patients based on survival outcomes and chemotherapy responses, independent of established prognostic parameters.</p><p><strong>Conclusion: </strong>This study uncovers a previously unrecognized TAM subtype that drives poor prognosis in BC. The identification of M_Macrophage-SPP1-C1Q enhances our understanding of TAM heterogeneity within the TME and offers a novel prognostic biomarker. The Macro.RF model provides a robust tool for predicting clinical outcomes and guiding personalized treatment strategies in BC patients.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"119"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728706","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":"Breast cancer scoring based on a multiplexed profiling of soluble and cell-associated (immune) markers facilitates the prediction of pembrolizumab therapy.","authors":"Verena Schweihofer, Christina Bruss, Stephan Seitz, Gunther Glehr, Madeleine Hetterich, Florian Weber, Maria Hatzipanagiotou, Miriam Fernández-Pacheco Álvarez, Olaf Ortmann, Gero Brockhoff, Richard J Bauer, Anja Kathrin Wege","doi":"10.1186/s12935-025-03729-7","DOIUrl":"10.1186/s12935-025-03729-7","url":null,"abstract":"<p><strong>Background: </strong>The immune checkpoint targeting is nowadays an integral part of cancer therapies. However, only a minority of patients experience long-term benefits. Thus, the identification of predictive biomarkers contributing to therapy response is urgently needed.</p><p><strong>Methods: </strong>Here, we analyzed different immune and tumor specific expression and secretion profiles in the peripheral blood and tumor samples of 50 breast cancer patients by multicolor flow cytometry and bead-based immunoassays at the time of diagnosis. Due to individual phenotype variations, we quantitatively scored 25 expressed and secreted immune-associated (e.g., LAG-3, PD-1, TIM-3, CD27) and tumor relevant markers (e.g., PD-L1, CD44, MHC-I, MHC-II) in immune checkpoint-treated triple negative breast cancer patients based on the current literature. The calculated score divided the patients into individuals with predicted pCR (total score of > 0) or predicted residual disease (total score of ≤ 0). At the end of the neoadjuvant therapy, the truly achieved pathological complete response (pCR; end of observation) was determined.</p><p><strong>Results: </strong>The calculated score was 79% in accordance with the achieved pCR at the time of surgery. Moreover, the sensitivity was 83.3%, the specificity 76.9%, the positive predictive value 62.5%, and the negative predictive value 90.9%. In addition, we identified a correlation of PD-1 and LAG-3 expression between tumor-associated and peripheral immune cells, which was independent of the subtype. Overall, PD-1 was the most frequently expressed checkpoint. However, in a number of patient-derived tumors, additional checkpoints as LAG-3 and TIM-3 were substantially (co-)expressed, which potentially compromises anti-PD-(L)1 mono-therapy.</p><p><strong>Conclusions: </strong>This study represents a proof-of-principle to identify potential checkpoint therapy responders in advance at the time of diagnosis. The work was based on a scoring derived from a multiplexed marker profiling. However, larger patient cohorts need to be prospectively evaluated for further validation.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"120"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728704","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":"Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword.","authors":"Sina Kamrani, Reza Naseramini, Pouria Khani, Zahra Sadat Razavi, Hamed Afkhami, Mohammad Reza Atashzar, Farzad Nasri, Sajad Alavimanesh, Farzane Saeidi, Hossein Ronaghi","doi":"10.1186/s12935-025-03741-x","DOIUrl":"10.1186/s12935-025-03741-x","url":null,"abstract":"<p><p>Multiple myeloma (MM) is a hematological malignancy defined by the abnormal proliferation and accumulation of plasma cells (PC) within the bone marrow (BM). While multiple myeloma impacts the bone, it is not classified as a primary bone cancer. The bone marrow microenvironment significantly influences the progression of myeloma and its treatment response. Mesenchymal stromal cells (MSCs) in this environment engage with myeloma cells and other bone marrow components via direct contact and the secretion of soluble factors. This review examines the established roles of MSCs in multiple facets of MM pathology, encompassing their pro-inflammatory functions, contributions to tumor epigenetics, effects on immune checkpoint inhibitors (ICIs), influence on reprogramming, chemotherapy resistance, and senescence. This review investigates the role of MSCs in the development and progression of MM.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"117"},"PeriodicalIF":5.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718089","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":"Multiomic traits reveal that critical irinotecan-related core regulator FSTL3 promotes CRC progression and affects ferroptosis.","authors":"Chengyi Huang, Bufu Tang, Wenjuan Chen, Jinggang Chen, Huojun Zhang, Minghua Bai","doi":"10.1186/s12935-025-03753-7","DOIUrl":"10.1186/s12935-025-03753-7","url":null,"abstract":"<p><strong>Background: </strong>Irinotecan is a widely used chemotherapy drug in colorectal cancer (CRC). The evolution and prognosis of CRC involve complex mechanisms and depend on the drug administered, especially for irinotecan. However, the specific mechanism and prognostic role of irinotecan-related regulators remain to be elucidated.</p><p><strong>Methods: </strong>Data from public databases were used to explore the multiomic traits of irinotecan-related regulators through bioinformatics analysis. RT‒qPCR, western blotting, transmission electron microscopy and flow cytometry were used as experimental validations.</p><p><strong>Results: </strong>Iriscore (irinotecan-related score) was constructed based on irinotecan-related regulators, and a high iriscore predicted a poor prognosis, poor therapeutic response and the MSS/MSI-L status. Single-cell analysis revealed that FSTL3 and TMEM98 were mainly expressed in CRC stem cells. Potential transcription factors (E2F1, STAT1, and TTF2) and therapeutic drugs (telatinib) that target irinotecan-related regulators were identified. FSTL3 was the core risk irinotecan-related regulator. Some ferroptosis regulators (GPX4, HSPB1 and RGS4) and related metabolic pathways (lipid oxidation and ROS metabolism) were correlated significantly with FSTL3. In vitro, irinotecan inhibited the expression of FSTL3 and ferroptotic defence proteins (GPX4 and SLC7A11), and induced lipid peroxidation and intracellular Fe (2+) ions concentration increased.</p><p><strong>Conclusions: </strong>We confirmed that irinotecan-related regulators, especially FSTL3, have effective prognostic value in CRC and speculated that FSTL3 may promote CRC progression and affect ferroptosis, which is beneficial for identifying candidate targeted irinotecan-related regulators and accurate individualized treatment strategies for CRC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"115"},"PeriodicalIF":5.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718091","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":"The miR-876-5p/SOCS4/STAT3 pathway induced the expression of PD-L1 and suppressed antitumor immune responses.","authors":"Hsuan-Yu Peng, Yu-Li Huang, Ping-Hsiu Wu, Li-Jie Li, Bou-Yue Peng, Chia-Yu Wu, Yu-Lung Lin, Michael Hsiao, Jang-Yang Chang, Peter Mu-Hsin Chang, Hsin-Lun Lee, Wei-Min Chang","doi":"10.1186/s12935-025-03704-2","DOIUrl":"10.1186/s12935-025-03704-2","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) remains a formidable challenge due to its high recurrence rates and poor prognosis. This study focuses on miR-876, a microRNA significantly associated with OSCC recurrence and clinical outcomes. Analysis of miRNA expression profiles from recurrent OSCC patients revealed that miR-876-5p is markedly upregulated in recurrent tumor tissues and the high expression of miR-876-5p correlates with reduced disease-free and overall survival. Functional assays demonstrated that miR-876 enhances OSCC cell growth, migration, and stemness, contributing to chemoresistance. Mechanistically, miR-876-5p directly targets SOCS4, leading to increased STAT3 activation and subsequent upregulation of PD-L1, which facilitates immune evasion. Additionally, exposure to the tobacco-specific carcinogen NNK was found to induce miR-876 expression and STAT3 activation, implicating environmental factors in miR-876 regulation and promote cancer recurrent. These findings identify the miR-876-5p-SOCS4-STAT3 axis as a critical pathway in OSCC progression, highlighting miR-876-5p as a potential biomarker and therapeutic target to improve treatment outcomes in OSCC patients.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"114"},"PeriodicalIF":5.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718094","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}