Oncology Letters最新文献

{"title":"ARID3A knockdown facilitates ferroptosis partly through modulation of the PTEN/Akt pathway in breast cancer.","authors":"Pengfei Shi, Yan Yi, Maojie Zhang, Yongjun Liu, Ming Jiang, Jiaming Zhang","doi":"10.3892/ol.2026.15733","DOIUrl":"10.3892/ol.2026.15733","url":null,"abstract":"<p><p>AT-rich interaction domain 3A (ARID3A) is a tumor regulator that modifies the PTEN and Akt pathway. The present study aimed to investigate the effect of ARID3A knockdown on ferroptosis and the interaction between ARID3A and the PTEN/Akt pathway in breast cancer. Firstly, MCF-7 and MDA-MB-231 cell lines were cultured. Negative control small interfering RNA (siNC) and ARID3A small interfering RNA (siARID3A) were transfected into the cells. Subsequently, siNC, PTEN small interfering RNA (siPTEN) and siARID3A were transfected into the cells alone or in combination. Comprehensive ferroptosis-associated indices were assessed. siARID3A transfection decreased cell viability, mitochondrial membrane potential (MMP) and glutathione peroxidase 4 (GPX4) expression, but increased the levels of malondialdehyde, reactive oxygen species (ROS) and ferrous iron (Fe²⁺), suggesting that siARID3A transfection promoted ferroptosis. Furthermore, siARID3A transfection upregulated PTEN expression and downregulated phosphorylated (p)-Akt levels, while siPTEN transfection elevated p-Akt levels and attenuated the effect of siARID3A transfection on p-Akt levels, indicating that siARID3A transfection modified the PTEN-mediated Akt pathway. In addition, siPTEN transfection increased cell viability, MMP and GPX4 expression, while decreasing ROS and Fe²⁺ levels. siPTEN transfection weakened the effect of siARID3A transfection on the majority of the aforementioned ferroptosis-associated indices, suggesting that PTEN was implicated in the function of ARID3A in ferroptosis. Overall, ARID3A knockdown promoted ferroptosis partly through modulation of the PTEN/Akt pathway in breast cancer. Despite this, further verification is still needed in future studies.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 2","pages":"378"},"PeriodicalIF":2.1,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412367","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 impact of low skeletal muscle mass in stage I-III colon cancer: A retrospective study.","authors":"Chen Mi, Feng Cui, Hanteng Yang","doi":"10.3892/ol.2026.15731","DOIUrl":"10.3892/ol.2026.15731","url":null,"abstract":"<p><p>Colon cancer (CC) is a common malignancy. Although the TNM staging system is widely employed for prognosis, its ability to predict individual patient outcomes is limited. In recent years, however, low skeletal muscle mass (SM) has emerged as a marked prognostic factor in patients with cancer. The present study aimed to investigate the prognostic value of low SM in patients with stage I-III CC. The present retrospective analysis included 230 patients with CC who underwent tumor resection at Lanzhou University Second Hospital (Lanzhou, China). The skeletal muscle index (SMI) was assessed using preoperative abdominal CT scans. Patients were stratified into low SM and non-sarcopenia groups based on their SMI. The primary outcome was overall survival (OS). The prognostic significance of low SM was evaluated using Kaplan-Meier survival curves, Cox regression modeling and time-dependent receiver operating Characteristic analysis. Furthermore, a combined TNM and low SM model was developed. Among the 230 patients, results showed that 24.34% exhibited low SM. Kaplan-Meier curves indicated that patients in the low SM group exhibited significantly lower OS rates compared with the normal SM group (P<0.001). Cox regression identified low SM as an independent adverse prognostic factor (hazard ratio: 1.70; 95% CI: 1.05-2.75). Incorporating low SM into the TNM model increased the Harrell's C-index from 0.570 to 0.604 (likelihood ratio P=0.027), with improved predictive performance at 1, 3 and 5-year time points. Overall, the present study concluded that low SM was an independent prognostic factor for OS in patients with stage I-III CC and a valuable supplement to existing prognostic tools, further contributing to personalized treatment strategies.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 2","pages":"376"},"PeriodicalIF":2.1,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412401","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":"A genome-wide Mendelian randomization study focusing on endoplasmic reticulum stress reveals novel genetic markers for renal cell carcinoma.","authors":"Bingli Gao, Zhaojun Li, Jihan Shi, Junwen Shen","doi":"10.3892/ol.2026.15732","DOIUrl":"10.3892/ol.2026.15732","url":null,"abstract":"<p><p>The causal association between endoplasmic reticulum stress and renal cell carcinoma remains poorly defined. The present study aimed to identify potential causal relationships between endoplasmic reticulum (ER) stress-related genes and renal cell carcinoma (RCC) by integrating multi-omics datasets using summary data-based Mendelian randomization (SMR). Data on the methylation, expression and protein levels of ER stress-related genes were obtained from quantitative trait loci studies. Genetic associations with RCC were derived from 11 studies comprising 5,219 RCC cases of European descent. SMR and colocalization analyses were performed to assess correlations and identify shared causal genetic variants. Molecular experiments were conducted for validation. In total, 1,193 ER stress-related genes were identified. SMR analysis revealed 3 DNA methylation probes (cg07431106, cg12446953 and cg08884395), 1 gene (polycystin 1) and 3 protein probes (SeqId_4125_52, SeqId_3448_13 and SeqId_17161_1) as key causal variants for RCC (SMR, P<0.01; Heterogeneity In Dependent Instruments, P>0.01). Bayesian colocalization analysis corroborated a strong causal relationship for all 7 variables (posterior probability for H4 >0.7). Multi-omics data integration identified PTEN induced kinase 1 as a protective factor and estrogen receptor 1 as a progression factor in RCC. Molecular experiments demonstrated that ER stress may be a mechanism for RCC progression and sunitinib resistance. The 7 key variables showed significant differences in an RCC cell line model, supporting the SMR results. In conclusion, the results of the present study suggested a potential association between ER stress and RCC. SMR analysis identified 3 cytosine-phosphate-guanine sites, 1 gene and 3 protein sites as causal variants associated with RCC.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 2","pages":"377"},"PeriodicalIF":2.1,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13347009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148423023","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":"Association between fibroblast activation protein α expression and immune environment in gastric cancer.","authors":"Kosuke Kubo, Yukinori Kurokawa, Takaomi Hagi, Shinnosuke Nagano, Tsuyoshi Takahashi, Takuro Saito, Kazuyoshi Yamamoto, Kota Momose, Kotaro Yamashita, Koji Tanaka, Tomoki Makino, Kiyokazu Nakajima, Hidetoshi Eguchi, Yuichiro Doki","doi":"10.3892/ol.2026.15730","DOIUrl":"10.3892/ol.2026.15730","url":null,"abstract":"<p><p>Tumor stroma serves an important role in cancer progression. However, the role of fibroblast activation protein α (FAP), a subpopulation marker of cancer-associated fibroblasts (CAFs), remains poorly understood, especially in gastric cancer. The present study investigated the role of FAP-positive CAFs in gastric cancer prognosis and immune environment. The retrospective study included patients with gastric cancer who underwent curative resection. The tumor-stroma ratio (TSR) and FAP expression status were evaluated using immunohistochemistry, after which their associations with recurrence-free survival (RFS) were investigated. In addition, immune cell infiltration was evaluated, including T cells, regulatory T cells (Tregs) and M2 macrophages, using immunohistochemistry, and its association with TSR or FAP status was analyzed. Among the 128 eligible patients, 29 (23%) had low TSR, whereas 39 (30%) were FAP-positive. No significant association was observed between TSR and FAP status (P=0.596). The low TSR group and FAP-positive group showed significantly worse survival than the high TSR group and FAP-negative group (log-rank P=0.004, P=0.011, respectively). Subsequently, a Cox multivariate analysis for RFS identified that FAP positivity was an independent factor for poor prognosis (P=0.009) but low TSR was not (P=0.088). FAP-positive patients had a higher tumor infiltrating FOXP3⁺ Tregs/CD3⁺ T-cell ratio (P<0.001) and FOXP3⁺ Tregs/CD8⁺ T-cell ratio (P=0.006), and higher levels of CD163⁺ M2 macrophages (P=0.011) compared with FAP-negative patients, although such differences were not observed according to TSR status. In conclusion, the present study revealed that FAP status may be an independent prognostic factor in gastric cancer, potentially contributing to the formation of immune tolerance within the tumor microenvironment.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 2","pages":"374"},"PeriodicalIF":2.1,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412374","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":"Clinicopathological features and therapeutic advances in primary pulmonary lymphoepithelioma-like carcinoma (Review).","authors":"Yong Chen, Yonglin Yu, Xiaoju Chen","doi":"10.3892/ol.2026.15728","DOIUrl":"10.3892/ol.2026.15728","url":null,"abstract":"<p><p>Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare subtype of non-small cell lung cancer, the clinicopathological features and molecular mechanisms of which are markedly different from those of other lung cancer subtypes. In recent years, with in-depth research in molecular pathology and immunology, notable progress has been achieved in the pathogenesis, diagnostic methods and therapeutic strategies of PPLELC. Epidemiological studies have shown that PPLELC is closely associated with Epstein-Barr virus (EBV) infection and the role of EBV in tumorigenesis has become a particular research focus. In addition, the unique immune microenvironment characteristics of PPLELC provide potential targets for immunotherapy. The present review systematically summarizes the epidemiology, pathological features, molecular biological mechanisms and diagnostic methods of PPLELC and focuses on discussing the association between EBV infection and tumorigenesis, the characteristics of immune microenvironment, as well as the latest advances in targeted therapy and immunotherapy. The aim was to provide a comprehensive diagnostic and therapeutic framework for clinicians and to prospect future research directions.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 2","pages":"373"},"PeriodicalIF":2.1,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13339021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405466","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":"Superior cancer detection with transperineal biopsy in patients with an elevated prostate-specific antigen level and a PI-RADS score of 3-4: A retrospective cohort study.","authors":"Jun Zhang, Hui Zheng","doi":"10.3892/ol.2026.15729","DOIUrl":"10.3892/ol.2026.15729","url":null,"abstract":"<p><p>The early and accurate detection of prostate cancer remains pivotal for improving clinical outcomes. The present study aimed to compare the cancer detection rates (CDRs) and safety profiles of transperineal (TP) vs. transrectal (TR) prostate biopsy techniques in patients with elevated prostate-specific antigen (PSA) levels and magnetic resonance imaging findings suggestive of malignancy (Prostate Imaging Reporting and Data System score 3 or 4). A retrospective cohort study was conducted on 127 patients who underwent TP (n=65) or TR (n=62) prostate biopsies between May 2022 and August 2024. CDR, adverse events and laboratory findings were compared between the groups. The TP approach yielded a significantly higher CDR (55.38%) than the TR approach (27.42%) (P=0.001), with no increase in adverse events, such as fever, infection or rectal bleeding. Routine lab values, including those for PSA and free PSA, showed no significant differences. In conclusion, in the present retrospective single-center cohort, the TP protocol used was associated with a higher cancer detection rate than the TR protocol, without an increased rate of adverse events. Given the non-randomized design and protocol differences between groups, these findings should be interpreted with caution and warrant confirmation in prospective multicenter studies.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 2","pages":"375"},"PeriodicalIF":2.1,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13339007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405404","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":"Methylation of the <i>BMP6</i>, <i>BRCA1</i>, <i>ESR2</i>, <i>GSTP1</i> and <i>TIMP3</i> genes in Mexican women with breast cancer and benign disease.","authors":"Samantha Rebeca de la Torre-Guzmán, Andrea Marlene García Muro, Brenda Pelayo-Chávez, Carolina Vázquez-Gastélum, Martha Patricia Gallegos-Arreola, Ernesto Soto-Reyes, Sergio Osvaldo Meza-Chavolla, Josefina Yoaly Sánchez-López","doi":"10.3892/ol.2026.15723","DOIUrl":"10.3892/ol.2026.15723","url":null,"abstract":"<p><p>Breast cancer (BC) is the main cause of cancer-related mortality in women and is influenced by genetic, environmental and lifestyle factors. The inactivation of tumor suppressor genes, such as bone morphogenetic protein 6 (<i>BMP6</i>), breast cancer susceptibility gene 1 (<i>BRCA1</i>), estrogen receptor 2 (<i>ESR2</i>), glutathione S-transferase π1 (<i>GSTP1</i>) and tissue inhibitor of metalloproteinase 3 (<i>TIMP3</i>), via methylation may contribute to the development of BC. The present study analyzed the methylation status of these genes in 60 BC and benign disease (BD) tissue samples from Mexican women and the association with clinical and histopathological variables. DNA was modified with sodium bisulfite, followed by methylation-specific PCR and electrophoresis, and analyzed using χ² test, Fisher's exact test, logistic regression, odds ratio (OR) with 95% confidence interval and Kaplan-Meier curves. The results indicated that the average age was higher in the BC group compared with that in the BD group (55 vs. 42 years; P<0.00001), with ≥50 years being a significant risk factor (OR, 5.44; P=0.00002). Only <i>BRCA1</i> demonstrated a significant difference in methylation status, increasing the susceptibility to BC (OR, 2.50; P=0.0001), and tending to be associated with increased proliferation and lymph node metastasis. <i>TIMP3</i> methylation was significantly associated with distant metastasis (OR, 8.65; P=0.028). Methylation of <i>BRCA1</i> and <i>TIMP3</i> demonstrated a significant association with poor prognosis in BC. <i>BRCA1</i> was methylated more frequently in women with BC and <i>TIMP3</i> was associated with a higher risk of distant metastasis. The present study highlighted the potential of these genes as prognostic biomarkers and the need to further explore DNA methylation for diagnostic and therapeutic purposes in future research.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 2","pages":"368"},"PeriodicalIF":2.1,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376520","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":"Overexpression of EZH2 is associated with clinicopathological parameters and poor prognosis in gliomas.","authors":"Can Peng, Wei Chen, Jun Yang, Li Wang, Lixia Lu, Rong Ge","doi":"10.3892/ol.2026.15721","DOIUrl":"10.3892/ol.2026.15721","url":null,"abstract":"<p><p>The histone methyltransferase enhancer of zeste homolog 2 (EZH2), which is primarily localized in the nucleus, mediates Polycomb repressive complex activity by trimethylating lysine 27 of histone H3 (H3K27me3), thereby leading to transcriptional silencing. EZH2 plays a crucial role in cell proliferation, differentiation and apoptosis. Its overexpression is frequently observed in various cancers and contributes to tumor progression. A potential prognostic role for EZH2 in glioma has been suggested. The present study aimed to evaluate the clinicopathological and prognostic significance of EZH2 expression in glioma. EZH2 mRNA levels in tumor and normal tissues were assessed using the TIMER2.0 and The Cancer Genome Atlas databases. The prognostic value of EZH2 mRNA expression was analyzed using the Kaplan-Meier plotter. Immunohistochemistry was performed on 147 clinical glioma samples to evaluate EZH2 protein expression. Cox proportional hazards models and Kaplan-Meier survival curves were used to examine the associations between EZH2 expression, clinicopathological parameters and overall survival (OS). EZH2 was significantly upregulated and amplified in tumor tissues across multiple cohorts. In high-grade gliomas, elevated EZH2 expression was significantly associated with poorer OS, disease-specific survival and progression-free interval. The results of the present study indicated that EZH2 expression may serve as a valuable prognostic biomarker in glioma.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 2","pages":"366"},"PeriodicalIF":2.1,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376463","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":"Identification of neoadjuvant chemoradiotherapy resistance-associated proteins in locally advanced rectal cancer: A pilot study.","authors":"Jiang-Yi He, Yan Dong, Can Chen, Fang-Hao Lu, Feng-Wei Ran, Qiong Ding, Yun Du, Tao-Rui Liu, Yu-Ying Zhang, Teng Wang, Yu-Han Chen, Xiang Zhao, Sen-Lin Xu, Jian-Jun Li","doi":"10.3892/ol.2026.15722","DOIUrl":"10.3892/ol.2026.15722","url":null,"abstract":"<p><p>Neoadjuvant chemoradiotherapy (nCRT) resistance in locally advanced rectal cancer (LARC) leads to worse outcomes. The present pilot study aimed to identify candidate proteins associated with resistance to nCRT. Data-independent acquisition mass spectrometry on 15 formalin-fixed paraffin-embedded tumor tissues, collected before and after nCRT, from four nCRT-resistant and four nCRT-sensitive LARC cases, was performed, identifying 6,006 proteins. Before nCRT, 133 proteins were found to be more abundant in resistant tumors and were preliminarily enriched in cell junction and metabolic pathways. After nCRT, 290 proteins were found to be more abundantly expressed in resistant tumors and were preliminarily enriched in pathways associated with DNA replication, transcription, translation and metabolism. Combined analysis of datasets GSE209746 and PXD060201 prioritized branched-chain keto acid dehydrogenase E1 subunit α (BCKDHA) as a candidate resistance-associated protein. In a colorectal cancer (CRC) tissue microarray, upregulated BCKDHA expression was associated with shorter overall survival, supporting its broader clinical relevance in CRC. In SW480 cells, BCKDHA overexpression increased clonogenic survival following irradiation, whereas BCKDHA knockdown enhanced radiosensitivity. These changes were accompanied by altered ataxia telangiectasia mutated, checkpoint kinase 2, DNA repair protein RAD51 homolog 1-associated signaling and γ-H2A histone family member X dynamics after irradiation. Collectively, these data identified BCKDHA as a candidate nCRT resistance-associated protein in LARC and provided preliminary functional evidence associating BCKDHA with the response to radiotherapy and DNA damage response-associated signaling. Further validation in larger pretreatment LARC cohorts and more direct mechanistic studies is warranted.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 2","pages":"367"},"PeriodicalIF":2.1,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376449","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":"SUMOylation inhibitor TAK-981 suppresses proliferation and induces apoptosis in SK-UT-1B uterine leiomyosarcoma cells.","authors":"Hosouk Joung, Hyunju Liu","doi":"10.3892/ol.2026.15724","DOIUrl":"10.3892/ol.2026.15724","url":null,"abstract":"<p><p>Uterine leiomyosarcoma (Ut-LMS) is an aggressive smooth muscle malignancy with limited therapeutic options and a poor prognosis, underscoring the need for new molecularly-targeted therapies. TAK-981 (subasumstat), a selective inhibitor of small ubiquitin-like modifier (SUMO)-activating enzymes, exhibits antitumor activity in several types of cancer; however, to the best of our knowledge, its therapeutic potential in Ut-LMS has not been explored. The current study evaluated the effects of TAK-981 on human Ut-LMS cells and revealed that SK-UT-1B cells exhibited markedly greater sensitivity to TAK-981 than SK-UT-1 cells. TAK-981 substantially reduced SK-UT-1B cell viability in a time- and concentration-dependent manner, whereas SK-UT-1 cells demonstrated a minimal response to TAK-981 at similar doses. Annexin V staining confirmed that TAK-981 induced the apoptosis of SK-UT-1B cells after 48 h, with apoptotic populations increasing proportionally with drug concentration. Furthermore, TAK-981 induced G₀/G₁ cell cycle arrest and markedly decreased Ki67 expression, indicating suppressed proliferative activity. TAK-981 also triggered substantial intracellular reactive oxygen species (ROS) accumulation and mitochondrial membrane depolarization, and antioxidant co-treatment demonstrated that apoptosis was partially ROS-dependent. Western blotting indicated robust inhibition of SUMO2/3 conjugation and activation of apoptotic markers, including cleaved caspase-3 and poly (ADP-ribose) polymerase, with the upregulation of p21 and p53. By contrast, autophagy markers, such as LC3B and p62, were unchanged, indicating that TAK-981 exerted its cytotoxic effects independently of the autophagic pathway. Collectively, these findings suggested that TAK-981 suppressed proliferation and induced apoptosis in SK-UT-1B Ut-LMS cells, accompanied by SUMOylation inhibition, ROS-associated mitochondrial dysfunction, apoptosis and G₀/G₁ cell-cycle arrest, and may represent a promising therapeutic candidate for further investigation in Ut-LMS.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 2","pages":"369"},"PeriodicalIF":2.1,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13329716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148391378","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}