Translational Oncology最新文献

{"title":"Radiation from frequent whole-body CT scans induces systemic immunosuppression and immune activation of tumor tissue","authors":"Jigang Dong ,&nbsp;Chengrui Fu ,&nbsp;Minghao Li ,&nbsp;Zhongtang Wang ,&nbsp;Baosheng Li","doi":"10.1016/j.tranon.2025.102326","DOIUrl":"10.1016/j.tranon.2025.102326","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to elucidate the impact of repeated whole-body computed tomography (CT) scans on systemic immunity, the tumor immune microenvironment, and tumor control. This inquiry was prompted by clinical observations indicating a decrease in the levels of IFN-β and IFN-γ in patients' blood following whole-body CT scans.</div></div><div><h3>Methods</h3><div>A Lewis lung carcinoma (LLC) mouse model was established and divided into two groups: a control group and a group subjected to multiple whole-body CT scanning radiation (WBCTSs). The study monitored tumor growth trends across both groups and employed a comprehensive set of analytical techniques—including enzyme-linked immunosorbent assay (ELISA), flow cytometry analysis, immunohistochemistry, RNA sequencing, and single-cell sequencing—to assess differences in cytokine profiles (IFN-β and IFN-γ), proportions of key immune cells, and gene expression variations between the groups.</div></div><div><h3>Results</h3><div>Repeated CT scan radiation does not promote tumor progression. In tumor tissues subjected to multiple CT scans, an increase in the proportion of CD8+ T cells, elevated interferon levels, and up-regulation of genes associated with killing in CD8+ T cells and genes associated with Ifnb in macrophages were observed. In contrast, radiation from multiple whole-body CT scans resulted in a decrease in the proportion of CD8+ T cells in the blood and spleen, a decrease in serum interferon levels, and down-regulation of killing-related genes in CD8+ T cells.</div></div><div><h3>Conclusion</h3><div>Our results suggest that repeated whole-body CT scanning radiation induces systemic immunosuppression and immune activation in tumor tissues. Multiple repeated CT scans do not promote tumor progression.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102326"},"PeriodicalIF":5.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487599","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":"MIAT: A pivotal oncogenic long noncoding RNA tunning the hallmarks of solid malignancies","authors":"Monica M. Rostom ,&nbsp;Alaa A. Rashwan ,&nbsp;Christina D. Sotiropoulou ,&nbsp;Sama Z. Hozayen ,&nbsp;Abdelhamid M. Abdelhamid ,&nbsp;Miriam Mokhtar Abdelhalim ,&nbsp;Omar Eltahtawy ,&nbsp;Hadir M. Emara ,&nbsp;Noha M. Elemam ,&nbsp;Christos K. Kontos ,&nbsp;Rana A. Youness","doi":"10.1016/j.tranon.2025.102329","DOIUrl":"10.1016/j.tranon.2025.102329","url":null,"abstract":"<div><div>Long non-coding RNAs (LncRNAs) have emerged as intriguing players in cellular regulation, challenging the traditional view of non-coding RNAs as mere \"dark genome\". Non-coding DNA makes up most of the human genome and plays a pivotal role in cancer development. These RNA molecules, which do not code for proteins, have captivated researchers with their diverse and crucial roles in gene regulation, chromatin dynamics, and other cellular processes. In several physiological and pathological circumstances, lncRNAs serve critical functions. This review will tackle the complex function of the lncRNA myocardial infarction-associated transcript (MIAT) in various solid malignancies. A special emphasis would be directed on the correlation between cancer patients' clinicopathological features and the expression profile of MIAT. MIAT is a oncogenic regulator in many malignant tumors, where it can control the growth, invasion, metastasis, and resistance to death of cells. As a result, MIAT is thought to be a possible biomarker and therapeutic target for cancer patients. The biological functions, mechanisms and potential clinical implications of MIAT during carcinogenesis and finally the current possible therapeutic approaches targeting MIAT are also outlined in this review.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102329"},"PeriodicalIF":5.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508251","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 the specific characteristics of neuroendocrine prostate cancer: Immune status, hub genes and treatment","authors":"Jianqing Wang ,&nbsp;Yu Wang ,&nbsp;Huihui Zhou ,&nbsp;Guopeng Yu ,&nbsp;Huan Xu ,&nbsp;Dajun Gao ,&nbsp;Minglun Li ,&nbsp;Yuzhuo Wang ,&nbsp;Bin Xu","doi":"10.1016/j.tranon.2025.102320","DOIUrl":"10.1016/j.tranon.2025.102320","url":null,"abstract":"<div><div>Castration-resistant prostate cancer (CRPC) marks the advanced phase of prostate malignancy, manifested through two principal subtypes: castration-resistant adenocarcinoma (CRPC-adeno) and neuroendocrine prostate cancer (NEPC). This study aims to identify unique central regulatory genes, assess the immunological landscape, and explore potential therapeutic strategies specifically tailored to NEPC. We discovered 1444 differentially expressed genes (DEGs) distinguishing between the two cancer types and identified 12 critical hub genes. Notably, CHST1, MPPED2, and RIPPLY3 emerged as closely associated with the immune cell infiltration pattern, establishing them as top candidates. Prognostic analysis highlighted the potential critical roles of CHST1 and MPPED2 in prostate cancer development, findings corroborated through in vitro and in vivo assays. Moreover, we validated the functions and expression levels of CHST1, MPPED2, and RIPPLY3 in NEPC using cell lines, animal models and human tissues. In the final step, we found that imatinib might be the drug specific to NEPC, which was further confirmed by in vitro cell assay. Our results revealed the clinical characteristics, molecular features, immune cell infiltration pattern in CRPC-adeno and NEPC, and identified and confirmed CHST1, MPPED2, and RIPPLY3 as the critical genes in the development in prostate cancer and NEPC. We also predicted and validated imatinib as the potential specific drugs to NEPC.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102320"},"PeriodicalIF":5.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143480688","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":"Mucin 4 expression is associated with metastasis in triple-negative breast cancer and can be tackled by soluble TNF blockade, improving immunotherapy outcome","authors":"Florencia Mauro ,&nbsp;Sofia Bruni ,&nbsp;Agustina Dupont ,&nbsp;Aldana Schey ,&nbsp;Agustina Badalini ,&nbsp;Gloria Inurrigarro ,&nbsp;Silvina Figurelli ,&nbsp;Sabrina Barchuk ,&nbsp;Daniel Lopez Della Vecchia ,&nbsp;Ernesto Gil Deza ,&nbsp;Yanina Rivenson ,&nbsp;Agustin Nava ,&nbsp;Elmer Fernandez ,&nbsp;Alejandro Urtreger ,&nbsp;Rosalia Cordo Russo ,&nbsp;María Florencia Mercogliano ,&nbsp;Roxana Schillaci","doi":"10.1016/j.tranon.2025.102325","DOIUrl":"10.1016/j.tranon.2025.102325","url":null,"abstract":"<div><h3>Purpose</h3><div>Triple-negative breast cancer (TNBC) has the worst prognosis among breast cancers. Immunotherapy is a therapeutic option, but there is no biomarker to guide promising combination treatments. Mucin 4 (MUC4) favors metastasis in preclinical cancer models. This study evaluates the efficacy of soluble TNF (sTNF) neutralization to tackle MUC4 expression preventing metastasis in combination with immunotherapy, and the potential use of MUC4 as a prognostic and predictive biomarker in TNBC patients.</div></div><div><h3>Experimental Design</h3><div>To explore TNF modulation of MUC4 expression, a panel of TNBC cell lines was used. To assess the effect of sTNF blockade with a dominant negative molecule in combination with anti-PD-1 antibody on lung metastasis and overall survival (OS), 4T1 and LMM3 tumors were used. MUC4, PD-L1 and Ki-67 expression was evaluated by immunohistochemistry, and tumor infiltrating lymphocytes (TILs) were assessed by H&amp;E staining, in a cohort of 49 early TNBC patients treated with chemotherapy.</div></div><div><h3>Results</h3><div>TNF neutralization reduces MUC4 expression in TNBC cell lines. Only the combination of sTNF blockade with anti-PD-1 antibody prevents metastasis and increases mice survival. In early TNBC patients MUC4 expression is inversely associated with TILs presence and PD-L1 and Ki-67 expression. Finally, MUC4 is associated with metastasis and is an independent biomarker of poor OS.</div></div><div><h3>Conclusions</h3><div>We proved the existence of a sTNF/MUC4 axis in TNBC that can be actionable by sTNF neutralization, preventing metastasis. We suggest that MUC4 is a suitable biomarker to guide immunotherapy in TNBC, together with the administration of sTNF blocking drugs to improve outcome.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102325"},"PeriodicalIF":5.0,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463524","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":"RNF135 promotes the stemness of breast cancer cells by ubiquitinating and degrading DDX58","authors":"Anqi Hu ,&nbsp;Lin Zhang ,&nbsp;Lei Cao ,&nbsp;Haifeng Li ,&nbsp;Riqing Huang ,&nbsp;Xiaohong Zhou ,&nbsp;Yanxia Shi ,&nbsp;Baojiang Li","doi":"10.1016/j.tranon.2025.102321","DOIUrl":"10.1016/j.tranon.2025.102321","url":null,"abstract":"<div><h3>Background</h3><div>RING finger protein 135 (RNF135) is identified as a regulator in certain cancer types. However, its role and molecular mechanisms in breast cancer are still unclear.</div></div><div><h3>Methods</h3><div>Herein, we investigated the level of RNF135 in tumor tissues of breast patients using the online database and confirmed the data by real-time PCR and western blot analysis. The effects of RNF135 on stemness maintenance and migration/invasion capability of breast cells were investigated by sphere formation, flow cytometry, and transwell assays. Limiting dilution xenograft assay and metastatic model were applied to assess the implications of RNF135 in tumorigenesis, chemoresistance, and metastasis.</div></div><div><h3>Results</h3><div>Our results revealed that RNF135 was upregulated in tumor tissues of breast patients, especially in metastatic patients. Knockdown of RNF135 suppressed stemness, and migration/invasion capability of breast cancer cells. Conversely, RNF135 overexpression enhanced the stemness and migration/invasion ability of breast cancer cells. Limiting dilution xenograft and metastatic assays demonstrated that RNF135 was required for the self-renewal of CSCs to initiate breast cancer development and metastasis. Mechanistically, DDX58 was identified as the substrate of RNF135 and RNF135 could facilitated the ubiquitination and degradation of DDX58. Notably, overexpression of DDX58 rescued the promoting effects of RNF135 on the stemness and migration/invasion ability of breast cancer cells.</div></div><div><h3>Conclusions</h3><div>Overall, our results implied that RNF135 promotes the stemness of breast cancer cells by ubiquitinating and degrading DDX58 and targeting of RNF135/DDX58 axis might be a feasible method to suppress tumorigenesis and metastasis of breast cancer patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102321"},"PeriodicalIF":5.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453502","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":"Individualized tumor-reactive T cells exhibit a potent anti-tumor response in prostate cancer","authors":"Lianjun He ,&nbsp;Nanlin Jiao ,&nbsp;Xing Bao ,&nbsp;Yao Wu ,&nbsp;Xueyi Qian ,&nbsp;Weijie He ,&nbsp;Han Zhen ,&nbsp;Lei Tang ,&nbsp;Huimin Shao ,&nbsp;Dong Zhuo ,&nbsp;Houbao Huang ,&nbsp;Zhenyu Xu","doi":"10.1016/j.tranon.2025.102322","DOIUrl":"10.1016/j.tranon.2025.102322","url":null,"abstract":"<div><h3>Background</h3><div>Cellular immunotherapy exhibits promise in treating blood tumors. However, its application for solid tumors is impeded by their heterogeneity and complex microenvironments. The development of individualized multitarget therapy may be the key to overcoming the challenge of tumor heterogeneity.</div></div><div><h3>Methods</h3><div>To generate tumor-reactive T cells, we modified the conditional reprogramming primary cell culture method by to establish a primary prostate cancer cell culture approach, refer to as eCR (enhanced conditional reprogramming). Then, Tumor tissue–derived primary cells were physically lysed and loaded into dendric cells, which, in turn, were co-cultured with peripheral blood T cells to induced individualized tumor-reactive T cells.</div></div><div><h3>Results</h3><div>Our improved culture method could use a small amount of fresh or frozen tumor specimens (including biopsy specimens), which can be amplified in vitro while maintaining their original characteristics, without contamination by heterologous antigens. Furthermore, a series of in vitro and in vivo experiments revealed these tumor-reactive T cells exhibited specific and effective killing of tumor cells through their ability to recognize neoantigens in cancer.</div></div><div><h3>Conclusion</h3><div>In this study, we developed a protocol for the generation of tumor-responsive T cells based on autologous tumor antigens in patients with prostate cancer. This platform is characterized by its multitargeted, individualized, affordability, and minimal adverse effects, holding significant promise in the treatment of prostate cancer as well as other solid tumors.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102322"},"PeriodicalIF":5.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463415","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":"Thiostrepton suppresses intrahepatic cholangiocarcinoma progression via FOXM1-mediated tumor-associated macrophages reprogramming","authors":"Yu Li ,&nbsp;Yifan Jiang ,&nbsp;Rongliang Tong ,&nbsp;Bo Ding ,&nbsp;Jiangzhen Ge ,&nbsp;Keyi Du ,&nbsp;Jingqi Sun ,&nbsp;Zheng Tang ,&nbsp;Diyu Chen ,&nbsp;Jian Wu","doi":"10.1016/j.tranon.2025.102327","DOIUrl":"10.1016/j.tranon.2025.102327","url":null,"abstract":"<div><div>Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer with an extremely poor prognosis, highlighting the urgent need for new treatment options. Recent studies increasingly suggest that the Forkhead box M1 (FOXM1) transcription factor may serve as a candidate target for cancer immunotherapy. However, its role and the underlying molecular mechanisms in ICC remain not fully understood. Here, we identify thiostrepton (TST) as a potent FOXM1 inhibitor, capable of exerting “dual anti-tumor” effects in ICC. On one hand, TST effectively suppresses tumor cell proliferation and metastasis. On the other hand, TST treatment improves the tumor immune microenvironment by reprogramming tumor-associated macrophages (TAMs), thereby enhancing anti-tumor immune responses. Mechanistically, TST directly alleviates ICC progression by arresting the cell cycle, promoting apoptosis, and inhibiting the epithelial-mesenchymal transition (EMT) process. Furthermore, TST-treated tumor cells secrete cytokines that drive TAMs repolarization toward the tumor-suppressive M1 phenotype. Overall, our results indicate that FOXM1 can serve as a novel target for ICC immunotherapy. By targeting FOXM1, TST exerts “dual anti-tumor” effects and has the potential to become a promising immunotherapy agent for ICC patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102327"},"PeriodicalIF":5.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463714","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":"Mitochondrial metabolism-related features guiding precision subtyping and prognosis in breast cancer, revealing FADS2 as a novel therapeutic target","authors":"Yakun Kang ,&nbsp;You Meng ,&nbsp;Jiangdong Jin ,&nbsp;Yuhan Dai ,&nbsp;Fei Li ,&nbsp;Nuo Chen ,&nbsp;Hui Xie ,&nbsp;Yangyang Cui","doi":"10.1016/j.tranon.2025.102330","DOIUrl":"10.1016/j.tranon.2025.102330","url":null,"abstract":"<div><h3>Background</h3><div>Breast cancer is one of the most prevalent malignant tumors in women. Mitochondria, essential for cellular function, have altered metabolic activity in cancer cells, influencing tumor regulation and clinical outcomes. The connection between mitochondrial metabolism-related genes and breast cancer prognosis remains underexplored. This study aims to investigate the role of these genes in breast cancer by constructing risk models.</div></div><div><h3>Methods</h3><div>Breast cancer transcriptome data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and mitochondrial gene data were sourced from the MitoCarta3.01 database. Clustering analysis was conducted using the \"ConsensusClusterPlus\" package, followed by Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A prognostic model was built using Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) algorithms. Immune cell infiltration levels were assessed via CIBERSORT and MCPcounter algorithms. Validation of key gene expression was performed on breast cancer tissue specimens and cell models to explore their biological functions in breast cancer cells.</div></div><div><h3>Results</h3><div>The LASSO regression analysis of the TCGA BRCA dataset identified four prognosis-related mitochondrial metabolism genes: MYH11, LTF, FADS2, and PSPHP1. Validation using the GEO dataset confirmed that patients with high-risk scores (based on these four genes) had shorter overall survival compared to those with lower risk scores. Immunological analysis revealed that high-risk patients were less responsive to immunotherapy but more sensitive to conventional chemotherapies. This suggests that combining chemotherapy with immunotherapy might enhance T cell-based treatments. Univariate and multivariate Cox regression confirmed that the mitochondrial gene model was an independent predictor of overall survival, and a nomogram was developed to predict patient prognosis. Tissue validation showed consistent expression patterns with bioinformatic predictions. Functional assays confirmed that FADS2 was highly expressed in breast cancer cells, and its knockout significantly reduced cell invasion, migration, and colony formation.</div></div><div><h3>Conclusion</h3><div>This study reveals that mitochondrial metabolism-related genes are closely associated with breast cancer progression, clinical outcomes, and genetic alterations. The findings may offer new avenues for treatment strategies, early intervention, and prognosis prediction in breast cancer.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102330"},"PeriodicalIF":5.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463525","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":"M2-like tumor-associated macrophages may promote tumor progression in malignant pleural mesothelioma","authors":"Tetsuya Fukui ,&nbsp;Ryota Sumitomo ,&nbsp;Toshi Menju ,&nbsp;Masashi Kobayashi ,&nbsp;Hiroaki Sakai ,&nbsp;Hiroshi Date","doi":"10.1016/j.tranon.2025.102324","DOIUrl":"10.1016/j.tranon.2025.102324","url":null,"abstract":"<div><h3>Introduction</h3><div>Malignant pleural mesothelioma (MPM) is an aggressive malignancy with an unfavorable prognosis. Asbestos-activated macrophages may contribute to both oncogenesis and progression of MPM. This study aimed to clarify the biological and clinical significance of M2-like tumor-associated macrophages (TAMs) in MPM.</div></div><div><h3>Methods</h3><div>This retrospective study included 101 MPM patients who were diagnosed and started treatment between 1998 and 2010. The distribution of M2-like TAMs in the intratumoral and peritumoral regions was evaluated by immunohistochemistry using CD163 staining. Tumor proliferation was evaluated by Ki-67 staining.</div></div><div><h3>Results</h3><div>Intratumoral M2-like TAM density was significantly correlated with the pretreatment C-reactive protein level (<em>r</em> = 0.283, <em>P</em> = 0.004) and Ki-67 proliferation index (<em>r</em> = 0.498, <em>P</em> &lt; 0.001). Peritumoral M2-like TAM density was also significantly correlated with the pretreatment C-reactive protein level (<em>r</em> = 0.255, <em>P</em> = 0.010) and Ki-67 proliferation index (<em>r</em> = 0.435, <em>P</em> &lt; 0.001). Additionally, intratumoral M2-like TAM density was associated with histological subtype (<em>P</em> &lt; 0.001), with higher densities observed in sarcomatoid tumors compared to epithelioid tumors. The overall survival rate was significantly worse in the intratumoral and peritumoral M2-like TAM-high groups (<em>P</em> = 0.044 and <em>P</em> = 0.046, respectively), particularly in patients with advanced-stage MPM. Multivariable analysis identified peritumoral M2-like TAM status (hazard ratio = 1.700, 95 % confidence interval: 1.034–2.796, <em>P</em> = 0.037), clinical stage, and histology as significant prognostic factors for overall survival.</div></div><div><h3>Conclusions</h3><div>During MPM progression, M2-like TAMs may induce tumor cell proliferation and aggressiveness, contributing to the poor prognosis in MPM patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102324"},"PeriodicalIF":5.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445205","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":"Lnc-PHF3-3 aggravates the chemoresistance of osteosarcoma cells to doxorubicin via the miR-142-3p/HMGB1 axis","authors":"Jingyi Zhou ,&nbsp;Mengkai Yang ,&nbsp;Weisong Zhao ,&nbsp;He Zhang ,&nbsp;Lingling Cao ,&nbsp;Qi Li ,&nbsp;Gangyang Wang","doi":"10.1016/j.tranon.2025.102328","DOIUrl":"10.1016/j.tranon.2025.102328","url":null,"abstract":"<div><h3>Background</h3><div>Chemoresistance poses a significant challenge in the treatment of osteosarcoma (OS). Long non-coding RNAs (lncRNAs) have emerged as crucial regulators of cancer biology. Despite accumulating evidence linking dysregulation of lncRNAs to chemoresistance, the specific regulatory functions and complexities involved in lncRNA-mediated modulation of doxorubicin-based chemotherapy in OS remain understudied.</div></div><div><h3>Methods</h3><div>We examined expression levels of lncRNA Lnc-PHF3-3 and miR-142-3p in OS tissues and cell lines by lncRNA microarray profiling and qRT-PCR. Gain-of-function and loss-of-function assays were performed to examine the effect of lncRNA Lnc-PHF3-3 and miR-142-3p on chemoresistance of OS cells. Using fluorescence reporter and western blot assays, we also explored the possible mechanisms of Lnc-PHF3-3 in OS cells.</div></div><div><h3>Results</h3><div>This study aimed to investigate key lncRNAs associated with chemoresistance in OS and identify potential therapeutic targets for patients with chemoresistant OS. To identify chemoresistance-related lncRNAs, microarray analysis was conducted using drug-resistant/drug-sensitive OS cell lines and chemoresistant/chemosensitive OS tissues. Among the identified candidates, a novel lncRNA called Lnc-PHF3-3 was found to be upregulated in doxorubicin-resistant OS cell lines and chemoresistant OS patients. Functional characterization revealed that Lnc-PHF3-3 promoted doxorubicin resistance both in vitro and in vivo. Further investigation revealed that Lnc-PHF3-3 acted as a sponge for microRNA miR-142-3p, and overexpression of miR-142-3p resulted in reduced chemoresistance. Additionally, the high mobility group box 1 (HMGB1) gene was identified as a direct and functional target of miR-142-3p.</div></div><div><h3>Conclusions</h3><div>We conclude that Lnc-PHF3-3 contributes to doxorubicin resistance in OS by sequestering miR-142-3p and subsequently enhancing HMGB1 expression.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"53 ","pages":"Article 102328"},"PeriodicalIF":5.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437882","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}