OncoTargets and therapyPub Date : 2025-06-11eCollection Date: 2025-01-01DOI: 10.2147/OTT.S544657
{"title":"Traditional Chinese Medicine Xiaoai Jiedu Recipe Suppresses the Development of Hepatocellular Carcinoma via Regulating the microRNA-29a/Signal Transducer and Activator of Transcription 3 Axis [Retraction].","authors":"","doi":"10.2147/OTT.S544657","DOIUrl":"https://doi.org/10.2147/OTT.S544657","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.2147/OTT.S248797.].</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"735-736"},"PeriodicalIF":2.7,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317554","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}
OncoTargets and therapyPub Date : 2025-06-10eCollection Date: 2025-01-01DOI: 10.2147/OTT.S544936
{"title":"Crosstalk Between EGFR and Integrin Affects Invasion and Proliferation of Gastric Cancer Cell Line, SGC7901 [Retraction].","authors":"","doi":"10.2147/OTT.S544936","DOIUrl":"https://doi.org/10.2147/OTT.S544936","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.2147/OTT.S35322.].</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"733-734"},"PeriodicalIF":2.7,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310261","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":"Studying Immunogenic Cell Death in Human Colorectal Cancer Organoids.","authors":"Rebecca Lisandrelli, Matthias Winkler, Zlatko Trajanoski, Giorgia Lamberti","doi":"10.2147/OTT.S521346","DOIUrl":"10.2147/OTT.S521346","url":null,"abstract":"<p><strong>Purpose: </strong>Combination therapies of chemotherapeutic agents and immunotherapy have shown promising results in the treatment of cold tumors. Various chemotherapies trigger immunogenic cell death (ICD) and release of hallmarks immunogenic damage associated molecular patterns (DAMPs) that have been related with immunostimulatory activities, leading to better patient prognosis. We aim to optimize in vitro assays to detect DAMPs release in response to chemotherapeutic agents using a colorectal cancer (CRC) organoids model.</p><p><strong>Methods: </strong>CRC patient-derived organoids (PDOs) were treated either with oxaliplatin (OXA) or with 5-fluorouracil (5FU) and viability was measured with CellTiter-Glo3D Cell viability assay. Calreticulin (CALR) and high mobility group box 1 protein (HMGB1) intracellular translocation was assessed in immunofluorescence microscopy and quantified via co-localization with wheat germ agglutinin (WGA) and DAPI. Extracellular release of adenosine triphosphate (ATP) was quantified via specific luminescence assays.</p><p><strong>Results: </strong>The results showed that CRC PDOs release DAMPs in a patient-specific manner in response to OXA and 5FU treatments.</p><p><strong>Conclusion: </strong>This study successfully used immunofluorescence and luminescence methods to detect ICD-associated DAMPs release in CRC PDOs in response to chemotherapeutic treatments. This approach allows the recognition of patient-specific ICD activation and could help predict patient response to therapies.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"705-715"},"PeriodicalIF":2.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12152962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275526","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}
OncoTargets and therapyPub Date : 2025-06-06eCollection Date: 2025-01-01DOI: 10.2147/OTT.S516486
Liying Peng, Tiantian Shan, Xinyi Zhou, Zhongyuan Feng, Wanting Qiang, Jing Lu, Haiyan He, Juan Du
{"title":"Lowering the Selinexor Dose within the Pomalidomide and Dexamethasone Combination Regimen Elicits Fewer Side Effects While Comparable Efficacy Against Relapsed/Refractory Multiple Myeloma.","authors":"Liying Peng, Tiantian Shan, Xinyi Zhou, Zhongyuan Feng, Wanting Qiang, Jing Lu, Haiyan He, Juan Du","doi":"10.2147/OTT.S516486","DOIUrl":"10.2147/OTT.S516486","url":null,"abstract":"<p><strong>Background: </strong>As a novel oral Exportin 1 (XPO1) inhibitor, selinexor at 80 or 100 mg has demonstrated efficacy in treating relapsed/refractory multiple myeloma (RRMM), nonetheless, this dosage has shown poor tolerability.</p><p><strong>Objective: </strong>To explore the optimal dosage of selinexor, we evaluated the efficacy and safety of 60 vs 40 mg selinexor, combine with regimen comprising pomalidomide and dexamethasone in RRMM.</p><p><strong>Design: </strong>21 patients with RRMM were enrolled to receive selinexor (60 or 40 mg once weekly), together with pomalidomide (4 mg/day on days 1-21) and dexamethasone (40 mg once weekly); the SPD-60 group (6 patients) vs SPD-40 group (15 patients).</p><p><strong>Methods: </strong>The clinical response and efficacy of the two groups were continuously followed up, and statistical analysis was carried out to screen out the dose group with fewer side effects and better efficacy. The primary endpoint was (objective response rates) ORR. The secondary endpoints included treatment safety and tolerability, progression-free survival (PFS) and overall survival (OS).</p><p><strong>Results: </strong>The ORR of the SPD-60 and SPD-40 groups were 33.3% and 46.7% respectively (<i>P</i>=0.773). With a median follow-up of 20.9 months, the median PFS was 6.2 months and the median OS was not achieved across all treated patients. The median PFS for SPD-60 group was 4.3 months, while for SPD-40 was 8.0 months (<i>P</i>=0.618). The 1-year OS rate were 66.7% for SPD-60 group and 85.1% for the SPD-40 group (<i>P</i>=0.308). The most common hematological adverse events were neutropenia (SPD-60 group 50% vs SPD-40 group 53.3%) and thrombocytopenia (50% vs 46.7%). Fatigue (83.3% vs 40%), infection (50% vs 53.3%), and nausea (83.3% vs 40%) were the most common non-hematologic adverse effects.</p><p><strong>Conclusion: </strong>The SPD-40 regimen may be more clinically applicable than SPD-60, as it elicited fewer adverse effects while demonstrating equivalent efficacy.</p><p><strong>Trial registration: </strong><i>ClinicalTrials.gov</i>: NCT04941937.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"695-703"},"PeriodicalIF":2.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266870","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}
OncoTargets and therapyPub Date : 2025-06-05eCollection Date: 2025-01-01DOI: 10.2147/OTT.S499695
Hui Liu, Yongming Huang, Guanghua Fu, Bo Lei, Ke Liu
{"title":"IGFBP1 is One of 10 Metabolic Factors Predicting Recurrence Free Survival in Gastric Cancer and Promotes Cancer Progression via ZFX-IGFBP1 Axis.","authors":"Hui Liu, Yongming Huang, Guanghua Fu, Bo Lei, Ke Liu","doi":"10.2147/OTT.S499695","DOIUrl":"10.2147/OTT.S499695","url":null,"abstract":"<p><strong>Introduction: </strong>Metabolism-related genes (MRGs) critically influence cancer prognosis, yet their role in gastric carcinoma (GC) remains poorly understood.</p><p><strong>Methods: </strong>We analyzed 24,991 genes from 407 GC patients in TCGA to identify a metabolic gene-based prognostic signature. In vitro and in vivo functional experiments validated key findings, while transcriptional regulation mechanisms were explored through promoter interaction assays.</p><p><strong>Results: </strong>A robust 10-metabolic gene signature was identified as strongly predictive of recurrence-free survival (RFS) in GC. Elevated insulin-like growth factor binding protein 1 (IGFBP1) expression correlated with reduced overall survival and disease-free survival. Functional studies demonstrated IGFBP1's oncogenic role in promoting GC proliferation and metastasis. Mechanistically, zinc finger protein X-linked (ZFX) activated IGFBP1 transcription by directly binding to its promoter.</p><p><strong>Discussion: </strong>We established a prognostic nomogram integrating the 10-metabolic gene signature for GC RFS prediction. IGFBP1 emerges as a potential therapeutic target and biomarker, with ZFX-driven transcriptional activation as a novel regulatory axis in GC progression.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"717-732"},"PeriodicalIF":2.7,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12148340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258653","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}
OncoTargets and therapyPub Date : 2025-05-26eCollection Date: 2025-01-01DOI: 10.2147/OTT.S516982
Jiaofeng Shen, Guangyu Gao, Songtao Liu
{"title":"MAM Domain Containing 2 (MAMDC2) Affects Invasion and Metastasis of Human Gastric Cancer.","authors":"Jiaofeng Shen, Guangyu Gao, Songtao Liu","doi":"10.2147/OTT.S516982","DOIUrl":"10.2147/OTT.S516982","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is the fifth most prevalent cancer worldwide and the fourth leading cause of cancer-related mortality. MAM Domain Containing 2 (MAMDC2) has been involved in many cancers. However, the impact of MAMDC2 on gastric cancer was unclear. This study aimed to investigate the role and mechanism of MAMDC2 in gastric cancer.</p><p><strong>Methods: </strong>Differential genes in gastric cancer are analyzed by GEO, TCGA, MSigDB database, R-packet limma, and Wilcoxon test. Survival analysis is performed through the R package survival. Construct a PPI network through the STRING database. Enrichment analysis is performed by Metascape. The infiltration level of gastric cancer immune cells is calculated by CIBERSORT. In addition, the expression of MAMDC2 was analyzed by immunohistochemistry and quantitative real-time polymerase chain reaction (RT-qPCR). siMAMDC2 was used to knock down the specific gene. Cell counting kit-8 (CCK-8) assay, colony formation assay, and cell migration were applied to evaluate the function of MAMDC2 in gastric cancer cells.</p><p><strong>Results: </strong>In the present study, we revealed a significant upregulation of MAMDC2 in gastric cancer tissues and cells. Knocking down MAMDC2 inhibited the proliferation and migration of gastric cancer cells, while overexpression of MAMDC2 produced the opposite results. Furthermore, MAMDC2 may be an independent factor in poor prognosis in gastric cancer patients.</p><p><strong>Conclusion: </strong>These results illustrated that MAMDC2 promoted the proliferation and migration of gastric cancer cells. The newly identified MAMDC2 provides novel insight into the pathogenesis of gastric cancer.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"679-693"},"PeriodicalIF":2.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12124315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199764","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":"Validation of a Combined Prognostic Score Using Plasma Tumor DNA and Clinical Features in Metastatic Castration-Resistant Prostate Cancer Patients Treated with Taxanes.","authors":"Nicole Brighi, Giuseppe Schepisi, Vincenza Conteduca, Emanuela Scarpi, Paola Caroli, Federica Matteucci, Cristian Lolli","doi":"10.2147/OTT.S509285","DOIUrl":"10.2147/OTT.S509285","url":null,"abstract":"<p><strong>Purpose: </strong>There is an urgent need of biomarkers to personalize metastatic castration-resistant prostate cancer (mCRPC) treatment. A new prognostic model described by our group combines molecular characteristics (ptDNA levels), metabolic features from PET-scans (metabolic tumor volume), clinical parameters (visceral metastases), and lab tests (lactate-dehydrogenase levels) in abiraterone or enzalutamide-treated patients. This study aims to validate the score on mCRPC patients undergoing taxane treatment.</p><p><strong>Patients and methods: </strong>Twenty-eight patients affected by mCRPC, pre-treated with abiraterone or enzalutamide, candidate for taxane-based treatments, have been prospectively evaluated. All patients underwent a basal PET/CT scan with F-choline and blood samples. The prognostic model previously described was applied to this population; based on the partial results of the parameters, we assigned the patients into three risk groups.</p><p><strong>Results: </strong>In the 28 patients evaluated, we observed a different median OS among the three risk groups (risk group I, 18.1 months [95% CI: 15.2-33.1 months]; risk group II, 12.7 months [4.9-18.6 months]; and risk group III, 10.1 months [3.4-15.4 months]; p = 0.012). Statistically significant differences were also observed for PFS.</p><p><strong>Conclusion: </strong>The prognostic score has confirmed to be a good prognostic tool also in a more advanced cohort of patients treated with taxanes. This tool may represent a valid method to refine prognostication and treatment selection in a cohort of patients where biomarkers are scarce.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"667-677"},"PeriodicalIF":2.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174358","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}
OncoTargets and therapyPub Date : 2025-05-14eCollection Date: 2025-01-01DOI: 10.2147/OTT.S515119
Riyadi Wibowo, Yunia Sribudiani, Kiki Lukman, Reno Rudiman, Tommy Ruchimat, Bambang Am Am Setya Sulthana, Andriana Purnama, Alma Wijaya, Etis Primastari, Prapanca Nugraha
{"title":"CXCL11: A Novel Biomarker in Colorectal Cancer as Metastasis Predictor.","authors":"Riyadi Wibowo, Yunia Sribudiani, Kiki Lukman, Reno Rudiman, Tommy Ruchimat, Bambang Am Am Setya Sulthana, Andriana Purnama, Alma Wijaya, Etis Primastari, Prapanca Nugraha","doi":"10.2147/OTT.S515119","DOIUrl":"10.2147/OTT.S515119","url":null,"abstract":"<p><strong>Objective: </strong>CXCL11 (C-X-C motif chemokine ligand 11) encodes a chemokine, a small signaling protein involved in immune and inflammatory responses. This study aims to evaluate the association between CXCL11 gene expression variations and metastasis in colorectal cancer (CRC) patients, highlighting its potential as a biomarker for metastasis.</p><p><strong>Methods: </strong>This is observational laboratory-based study utilized tissue samples from colorectal cancer (CRC) patients stored in the Tissue Bank of the Research Unit, Division of Digestive Surgery, Faculty of Medicine, Universitas Padjadjaran. Conducted between January and August 2024, data collection involved pathological and anatomical assessments of tissue samples obtained through biopsies or tumor resections. Gene expression analysis was performed on 60 fresh tumor tissues using PCR at the Biomolecular Laboratory, Faculty of Medicine, Universitas Padjadjaran.</p><p><strong>Results: </strong>The findings revealed a significant variation in CXCL11 expression among CRC patients based on cancer stage (P = 0.015) and metastasis status (P = 0.017). However, no significant differences in CXCL11 expression were observed concerning age, gender, anatomical pathology, or tumor location.</p><p><strong>Conclusion: </strong>This study identifies a relationship between CXCL11 gene expression differences and metastasis in CRC patients. Further studies with larger sample sizes are recommended to validate CXCL11's role as a biomarker for CRC metastasis. Additionally, future research should explore the potential application of CXCL11 in antitumor therapy.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"657-665"},"PeriodicalIF":2.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094486","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}
OncoTargets and therapyPub Date : 2025-05-12eCollection Date: 2025-01-01DOI: 10.2147/OTT.S506778
Dao-Yong Liu, Yun Zhu, Qiang Xie, Jun Deng, Bang-Ling Chen
{"title":"Risk of Residual Axillary Lymph Node Macrometastasis in Early Breast Cancer PATIENTS with One Positive Macrometastasis Sentinel Lymph Node.","authors":"Dao-Yong Liu, Yun Zhu, Qiang Xie, Jun Deng, Bang-Ling Chen","doi":"10.2147/OTT.S506778","DOIUrl":"10.2147/OTT.S506778","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the risk factors for residual axillary lymph node macro-metastasis in early-stage breast cancer patients with a single macrometastasis sentinel lymph node (SLN).</p><p><strong>Methods: </strong>We retrospectively analyzed the clinical data of 119 breast cancer patients diagnosed between January 2018 and September 2023, each with one positive SLN stained with methylene blue, who subsequently underwent axillary lymph node dissection. The patients were divided into two groups based on the total number of SLNs identified: fewer than three and more than three. Fisher's exact test was used for statistical analysis between groups.</p><p><strong>Results: </strong>Among the 119 patients evaluated, 30 patients had a total of 2 sentinel lymph nodes, with 15 testing positive for residual axillary lymph nodes, yielding a positivity rate of 50.0%. Another 30 patients had 3 sentinel lymph nodes, with a positivity rate of 33.3%. An additional 32 patients each had 4 sentinel lymph nodes, with a positivity rate of 3.13%. Finally, 27 patients had 5 sentinel lymph nodes, with a 0% positivity rate. The positivity rate of axillary lymph nodes was significantly higher in the group with ≤ 3 sentinel lymph nodes (less SLN group) compared to the group with > 4 sentinel lymph nodes (more SLN group). Binary logistic regression analysis confirmed that the number of SLNs was the only significant predictor of residual lymph node macrometastasis.</p><p><strong>Conclusion: </strong>The number of sentinel lymph nodes (SLNs) is a key factor influencing the risk of residual axillary lymph node macrometastasis in early-stage breast cancer patients with one positive SLN. Identifying a higher number of SLNs (≥4) significantly lowers the risk of residual metastasis, supporting the use of thorough SLN mapping in these cases to improve patient outcomes.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"647-656"},"PeriodicalIF":2.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094487","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}
OncoTargets and therapyPub Date : 2025-05-09eCollection Date: 2025-01-01DOI: 10.2147/OTT.S514001
Lin Wang, Liming Zhao, Jialiang Liu, Pu Cheng, Mingyu Han, Zhaoxu Zheng
{"title":"lncSLERT Promotes Liver Metastasis in Colorectal Cancer by Down-Regulating HUNK Expression via RBM15-Mediated m6A Modification.","authors":"Lin Wang, Liming Zhao, Jialiang Liu, Pu Cheng, Mingyu Han, Zhaoxu Zheng","doi":"10.2147/OTT.S514001","DOIUrl":"https://doi.org/10.2147/OTT.S514001","url":null,"abstract":"<p><strong>Background: </strong>Metastasis is a hallmark of cancer and the leading cause of cancer-related mortality. However, the mechanism underlying liver metastasis in colorectal cancer (CRC) remains incompletely understood. This study explores the role of long non-coding RNA (lncRNA) SLERT in promoting CRC liver metastasis by downregulating HUNK expression.</p><p><strong>Methods: </strong>SLERT expression levels in CRC tissues were analyzed and correlated with patient survival outcomes. Functional assays, including migration and invasion assays, were performed to assess the impact of SLERT knockdown and overexpression on metastatic behavior. Mechanistic studies examined SLERT's interaction with the RNA-binding protein RBM15 and its effect on HUNK mRNA stability. The subcellular localization of SLERT was also determined.</p><p><strong>Results: </strong>SLERT was significantly upregulated in CRC tissues and associated with poor survival outcomes. Silencing SLERT inhibited CRC cell migration and invasion, whereas its overexpression enhanced these metastatic properties. Mechanistically, SLERT interacted with RBM15, impairing its ability to stabilize HUNK mRNA, leading to decreased HUNK expression and increased metastatic potential. SLERT was primarily localized in the cytoplasm, indicating its active role in gene regulation within the tumor microenvironment.</p><p><strong>Conclusion: </strong>LERT promotes liver metastasis in CRC by downregulating HUNK expression through RBM15-mediated mRNA destabilization. These findings suggest that SLERT could serve as a diagnostic biomarker and therapeutic target. Targeting SLERT or restoring HUNK expression may provide novel strategies to combat CRC liver metastasis and improve patient prognosis.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"631-646"},"PeriodicalIF":2.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079361","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}