BioFactors最新文献

{"title":"Deciphering potential molecular mechanisms in clear cell renal cell carcinoma based on the ubiquitin-conjugating enzyme E2 related genes: Identifying UBE2C correlates to infiltration of regulatory T cells","authors":"Xiaoqiang Feng, Zhenwei Wang, Meini Cen, Zongtai Zheng, Bangqi Wang, Zongxiang Zhao, Zhihui Zhong, Yesong Zou, Qian Lv, Shiyu Li, Li Huang, Hai Huang, Xiaofu Qiu","doi":"10.1002/biof.2143","DOIUrl":"10.1002/biof.2143","url":null,"abstract":"<p>Renal clear cell carcinoma (ccRCC) is a highly aggressive and common form of kidney cancer, with limited treatment options for advanced stages. Recent studies have highlighted the importance of the ubiquitin-proteasome system in tumor progression, particularly the role of ubiquitin-conjugating enzyme E2 (UBE2) family members. However, the prognostic significance of UBE2-related genes (UBE2RGs) in ccRCC remains unclear. In this study, bulk RNA-sequencing and single-cell RNA-sequencing data from ccRCC patients were retrieved from the Cancer Genome Atlas and Gene Expression Omnibus databases. Differential expression analysis was performed to identify UBE2RGs associated with ccRCC. A combination of 10 machine learning methods was applied to develop an optimal prognostic model, and its predictive performance was evaluated using area under the curve (AUC) values for 1-, 3-, and 5-year overall survival (OS) in both training and validation cohorts. Functional enrichment analyses of gene ontology and Kyoto Encyclopedia of Genes and Genomes were conducted to explore the biological pathways involved. Correlation analysis was conducted to investigate the association between the risk score and tumor mutational burden (TMB) and immune cell infiltration. Immunotherapy and chemotherapy sensitivity were assessed by immunophenoscore and tumor immune, dysfunction, and exclusion scores to identify potential predictive significance. In vitro, knockdown of the key gene UBE2C in 786-O cells by specific small interfering RNA to validate its impact on apoptosis, migration, cell cycle, migration, invasion of tumor cells, and induction of regulatory T cells (Tregs). Analysis of sc-RNA revealed that UBE2 activity was significantly upregulated in malignant cells, suggesting its role in tumor progression. A three-gene prognostic model comprising UBE2C, UBE2D3, and UBE2T was constructed by Lasoo Cox regression and demonstrated robust predictive accuracy, with AUC values of 0.745, 0.766, and 0.771 for 1-, 3-, and 5-year survival, respectively. The model was validated as an independent prognostic factor in ccRCC. Patients in the high-risk group had a worse prognosis, higher TMB scores, and low responsiveness to immunotherapy. Additionally, immune infiltration and chemotherapy sensitivity analyses revealed that UBE2RGs are associated with various immune cells and drugs, suggesting that UBE2RGs could be a potential therapeutic target for ccRCC. In vitro experiments confirmed that the reduction of UBE2C led to an increase in apoptosis rate, as well as a decrease in tumor cell invasion and metastasis abilities. Additionally, si-UBE2C cells reduced the release of the cytokine Transforming Growth Factor-beta 1 (TGF-β1), leading to a decreased ratio of Tregs in the co-culture system. This study presents a novel three-gene prognostic model based on UBE2RGs that demonstrates significant predictive value for OS, immunotherapy, and chemotherapy in ccRCC patients. The findings underscore","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suppression of colorectal cancer growth: Interplay between curcumin and metformin through DMT1 downregulation and ROS-mediated pathways","authors":"Hui-Yen Chuang,&nbsp;Hui-Wen Chan,&nbsp;Kuang-Chung Shih","doi":"10.1002/biof.2137","DOIUrl":"10.1002/biof.2137","url":null,"abstract":"<p>The rising incidence of colorectal cancer (CRC) poses significant healthcare challenges. This study explored the therapeutic potential of combined curcumin (CUR) and metformin (MET) treatment in CRC models. Our findings indicate that the combination treatment (COMB) effectively downregulates the expression of divalent metal transporter-1 (DMT-1), leading to a reduction in cell proliferation aligned with suppression of the pAKT/mTOR/Cyclin D1 signaling pathway. The COMB increased reactive oxygen species (ROS) production, triggering activation of the NRF2/KEAP1 pathway. This pathway elicits an antioxidant response to manage oxidative stress in CRC cell lines. Interestingly, the response of NRF2 varied between CT26 and HCT116 cells. Moreover, our study highlights the induction of apoptosis and autophagy, as evidenced by upregulations in Bax/Bcl-2 ratios and autophagy-related protein expressions. Notably, the COMB promoted lipid peroxidation and downregulated xCT levels, suggesting the induction of ferroptosis. Ferroptosis has been shown to activate autophagy, which helps eliminate cells potentially damaged by the increased oxidative stress. Furthermore, the COMB effectively diminished the migratory ability of CRC cells. In vivo experiments using CRC-bearing mouse models, the results confirmed the anti-tumor efficacy of the COMB, leading to substantial inhibition of tumor growth without inducing general toxicity. In conclusion, our study suggests that combining CUR with MET holds promise as a potential option for CRC treatment, with critical mechanisms likely involving ROS elevation, autophagy, and ferroptosis.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of miRNAs in breast cancer development and progression: Current research","authors":"Sachin Kumar,&nbsp;Abhishek Ranga","doi":"10.1002/biof.2146","DOIUrl":"10.1002/biof.2146","url":null,"abstract":"<p>Breast cancer, a complex and heterogeneous ailment impacting numerous women worldwide, persists as a prominent cause of cancer-related fatalities. MicroRNAs (miRNAs), small non-coding RNAs, have garnered significant attention for their involvement in breast cancer's progression. These molecules post-transcriptionally regulate gene expression, influencing crucial cellular processes including proliferation, differentiation, and apoptosis. This review provides an overview of the current research on the role of miRNAs in breast cancer. It discusses the role of miRNAs in breast cancer, including the different subtypes of breast cancer, their molecular characteristics, and the mechanisms by which miRNAs regulate gene expression in breast cancer cells. Additionally, the review highlights recent studies identifying specific miRNAs that are dysregulated in breast cancer and their potential use as diagnostic and prognostic biomarkers. Furthermore, the review explores the therapeutic potential of miRNAs in breast cancer treatment. Preclinical studies have shown the effectiveness of miRNA-based therapies, such as antagomir and miRNA mimic therapies, in inhibiting tumor growth and metastasis. Emerging areas, including the application of artificial intelligence (AI) to advance miRNA research and the “One Health” approach that integrates human and animal cancer insights, are also discussed. However, challenges remain before these therapies can be fully translated into clinical practice. In conclusion, this review emphasizes the significance of miRNAs in breast cancer research and their potential as innovative diagnostic and therapeutic tools. A deeper understanding of miRNA dysregulation in breast cancer is essential for their successful application in clinical settings. With continued research, miRNA-based approaches hold promise for improving patient outcomes in this devastating disease.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dose-dependent effects of anthocyanin-rich extracts on obesity-induced inflammation and gut microbiota modulation","authors":"Nicholas Vannuchi,&nbsp;Giovana Jamar,&nbsp;Veridiana Vera de Rosso,&nbsp;Luciana Pellegrini Pisani","doi":"10.1002/biof.2144","DOIUrl":"10.1002/biof.2144","url":null,"abstract":"<p>Obesity and its associated inflammatory state pose a significant health burden. Anthocyanins, bioactive compounds found in fruits and vegetables, have garnered interest in their potential to attenuate these conditions. Understanding the dose-dependent response of anthocyanins is essential for optimizing their therapeutic potential in preventing and managing obesity. This comprehensive review explores the current knowledge on the dose-dependent effects of anthocyanins on obesity in both human and animal models, analyzing the structure and mechanism of absorption of these compounds. The article also highlights the diverse mechanisms underlying anthocyanin action, the symbiosis between anthocyanins and gut microbiota impacting metabolite production, influencing diverse health outcomes, modulating cytokines, and activating anti-inflammatory pathways. Additionally, their impact on energy metabolism and lipid regulation is discussed, highlighting potential contributions to weight management through AMPK and PPARγ pathways. Despite promising results, dose-dependent effects are fundamental considerations, with some studies indicating less favorable outcomes at higher doses. Future research should focus on optimizing dosages, accounting for individual responses, and translating findings into effective clinical applications for obesity management.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into an indolicidin-derived low-toxic anti-microbial peptide's efficacy against bacterial cells while preserving eukaryotic cell viability","authors":"Jihyun Kim,&nbsp;Jieun Lee,&nbsp;Eunho Kang,&nbsp;Kyoungmin Lee,&nbsp;Kyungeun Lee,&nbsp;Yeongmi Cheon,&nbsp;Seongsoo Lee,&nbsp;Bokyung Kim,&nbsp;Young Ho Ko,&nbsp;Jin Hae Kim,&nbsp;Su Il In,&nbsp;Chang Hoon Nam","doi":"10.1002/biof.2145","DOIUrl":"10.1002/biof.2145","url":null,"abstract":"<p>Antimicrobial peptides (AMPs) are a current solution to combat antibiotic resistance, but they have limitations, including their expensive production process and the induction of cytotoxic effects. We have developed novel AMP candidate (peptide 3.1) based on indolicidin, among the shortest naturally occurring AMP. The antimicrobial activity of this peptide is demonstrated by the minimum inhibitory concentration, while the hemolysis tests and MTT assay indicate its low cytotoxicity. In optical diffraction tomography, red blood cells treated with peptide 3.1 showed no discernible effects, in contrast to indolicidin. However, peptide 3.1 did induce cell lysis in E. coli, leading to a reduced potential for the development of antibiotic resistance. To investigate the mechanism underlying membrane selectivity, the structure of peptide 3.1 was analyzed using nuclear magnetic resonance spectroscopy and molecular dynamics simulations. Peptide 3.1 is structured with an increased distinction between hydrophobic and charged residues and remained in close proximity to the eukaryotic membrane. On the other hand, peptide 3.1 exhibited a disordered conformation when approaching the prokaryotic membrane, similar to indolicidin, leading to its penetration into the membrane. Consequently, it appears that the amphipathicity and structural rigidity of peptide 3.1 contribute to its membrane selectivity. In conclusion, this study may lead to the development of Peptide 3.1, a promising commercial candidate based on its low cost to produce and low cytotoxicity. We have also shed light on the mechanism of action of AMP, which exhibits selective toxicity to bacteria while not damaging eukaryotic cells.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the dysregulation of genes associated with glucose and lipid metabolism in gastric cancer and their influence on immunity and prognosis","authors":"Yan Li,&nbsp;Zhaolin Zeng","doi":"10.1002/biof.2138","DOIUrl":"10.1002/biof.2138","url":null,"abstract":"<p>Gastric cancer (GC) is one of the most prevalent malignant tumors globally, characterized by a high mortality rate. The disruption of glucose and lipid metabolism plays a critical role in the occurrence and progression of GC. By integrating single-cell and bulk RNA sequencing data, we identified 135 marker genes associated with glucose and lipid metabolism in GC. Building on this, we conducted prognosis and immune-related analyses, followed by cluster analysis that depicted various molecular subtypes, elucidating their distinct molecular mechanisms and treatment strategies. This includes examining how genes related to glucose and lipid metabolism influence GC prognosis through immune pathways. Additionally, we established a clinical prognostic model characterized by THRAP3, KLF5, and ABCA1. Notably, the core target gene ABCA1 may serve as a prognostic and immunotherapy biomarker for GC.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of lysosome-related prognostic signature to predict the survival outcomes and selecting suitable drugs for patients with HNSCC","authors":"Bing Cao,&nbsp;Shanshan Gu,&nbsp;Zhisen Shen,&nbsp;Yuna Zhang,&nbsp;Yiming Shen","doi":"10.1002/biof.2140","DOIUrl":"10.1002/biof.2140","url":null,"abstract":"<p>Lysosomes are digestive organelles responsible for endocytosis and autophagy. Recently, the malignancy and invasiveness head and neck squamous cell carcinoma (HNSCC) has been increasingly studied with the role of lysosomes. A list of lysosome-related genes were obtained from MSigDB. A Spearman correlation and univariate Cox regression analyses combined with differential expression analysis were conducted to detect differentially expressed lysosome-related genes related to prognosis. The prediction of prognostic signature was evaluated by plotting survival curve, ROC, and by developing a nomogram. Immune subtypes, infiltration of immune cells, GSVA, TIDE, IC₅₀ of common chemotherapy and targeted therapy, GO, and KEGG function enrichment analyses were carried out to explore the immune microenvironment of the signature. We constructed a lysosome-related prognostic signature that could function as an independent prognostic indicator for patients with HNSCC. High-risk patients were better suited to receive Doxorubicin, Mitomycin C, Pyrimethamine, anti-PD-L1 and anti-CTLA-4 immunotherapy, whereas low-risk patients had sensitivity to Lapatinib. GO functional enrichment analysis showed that prognostic features were strongly associated with epidermis-related functions (e.g., epidermal cell differentiation, epidermal development, and keratinization). In addition, a KEGG function enrichment analysis revealed a potential relationship between the risk assessment model and cardiomyopathy. We constructed a prognostic signature based on lysosome-related genes and successfully predicted the survival outcome of HNSCC patients, which not only provides potential guidance for personalized treatment but also provides a new idea for precision treatment of HNSCC.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Navigating the immune landscape with plasma cells: A pan-cancer signature for precision immunotherapy","authors":"Bicheng Ye,&nbsp;Aimin Jiang,&nbsp;Feng Liang,&nbsp;Changcheng Wang,&nbsp;Xiaoqing Liang,&nbsp;Pengpeng Zhang","doi":"10.1002/biof.2142","DOIUrl":"10.1002/biof.2142","url":null,"abstract":"<p>Immunotherapy has revolutionized cancer treatment; however, predicting patient response remains a significant challenge. Our study identified a novel plasma cell signature, Plasma cell.Sig, through a pan-cancer single-cell RNA sequencing analysis, which predicts patient outcomes to immunotherapy with remarkable accuracy. The signature was developed using rigorous machine learning algorithms and validated across multiple cohorts, demonstrating superior predictive power with an area under the curve (AUC) exceeding 0.7. Notably, the low-risk group, as classified by Plasma cell.Sig, exhibited enriched immune cell infiltration and heightened tumor immunogenicity, indicating an enhanced responsiveness to immunotherapy. Conversely, the high-risk group showed reduced immune activity and potential mechanisms of immune evasion. These findings not only enhance understanding of the intrinsic and extrinsic immune landscapes within the tumor microenvironment but also pave the way for more precise, biomarker-guided immunotherapy approaches in oncology.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning models reveal ARHGAP11A's impact on lymph node metastasis and stemness in NSCLC","authors":"Xiaoli Wang,&nbsp;Yan Zhou,&nbsp;Xiaomin Lu,&nbsp;Lili Shao","doi":"10.1002/biof.2141","DOIUrl":"10.1002/biof.2141","url":null,"abstract":"<p>Most patients with non-small cell lung cancer (NSCLC) are diagnosed at an advanced stage of the disease, which complicates treatment due to a heightened risk of metastasis. Consequently, the timely identification of biomarkers associated with lymph node metastasis is essential for improving the clinical management of NSCLC patients. In this research, the WGCNA algorithm was utilized to pinpoint genes linked to lymph node metastasis in NSCLC. A cluster analysis was carried out to investigate how these genes correlate with the prognosis and the outcomes of immunotherapy for NSCLC patients. Following this, diagnostic and prognostic models were created and validated through various machine learning methodologies. The random forest technique highlighted the importance of ARHGAP11A, leading to an in-depth examination of its role in NSCLC. By analyzing 78 tissue chip samples from NSCLC patients, the study confirmed the association between ARHGAP11A expression, patient prognosis, and lymph node metastasis. Finally, the influence of ARHGAP11A on NSCLC cells was assessed through cell function experiments. This research utilized the WGCNA technique to identify 25 genes that are related to lymph node metastasis, clarifying their connections with tumor invasion, growth, and the activation of stemness pathways. Cluster analysis revealed significant associations between these genes and lymph node metastasis in NSCLC, especially concerning immunotherapy and targeted treatments. A diagnostic system that combines various machine learning approaches demonstrated strong efficacy in forecasting both the diagnosis and prognosis of NSCLC. Importantly, ARHGAP11A was identified as a key prognostic gene associated with lymph node metastasis in NSCLC. Molecular docking analyses suggested that ARHGAP11A has a strong affinity for targeted therapies within NSCLC. Additionally, immunohistochemical assessments confirmed that higher levels of ARHGAP11A expression correlate with unfavorable outcomes for NSCLC patients. Experiments on cells showed that reducing ARHGAP11A expression can hinder the proliferation, metastasis, and stemness traits of NSCLC cells. This investigation reveals the novel insight that ARHGAP11A may function as a potential biomarker connected to lymph node metastasis in NSCLC. Moreover, reducing the expression of ARHGAP11A has demonstrated the ability to diminish tumor stemness characteristics, presenting a promising opportunity for improving treatment strategies for this condition.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The carcinogenesis of esophageal squamous cell cancer is positively regulated by USP13 through WISP1 deubiquitination","authors":"An Wang,&nbsp;Youbo Wang,&nbsp;Qinyun Ma,&nbsp;Xiaofeng Chen","doi":"10.1002/biof.2139","DOIUrl":"10.1002/biof.2139","url":null,"abstract":"<p>The objective was to determine whether USP13 stabilizes WISP1 protein and contributes to tumorigenicity and metastasis in ESCC through the Wnt/CTNNB1 signaling pathway. ESCC cell lines (KYSE150 and TE10) were treated with the proteasome inhibitor MG-132, followed by siRNA screening of deubiquitinases (DUBs) to identify regulators of WISP1. Mass spectrometry, immunoprecipitation, and in vitro functional assays were conducted to explore the interaction between USP13 and WISP1 and to assess the effects of USP13 downregulation on cell proliferation, migration, invasion, epithelial–mesenchymal transition (EMT), and apoptosis. Additionally, in vivo experiments using mouse models were performed to evaluate the impact of USP13 knockdown on tumor growth and metastasis. USP13 was identified as a key regulator of WISP1, stabilizing its protein levels through deubiquitination. Downregulation of USP13 resulted in reduced WISP1 protein stability, decreased cell proliferation, migration, and EMT, and increased apoptosis in vitro. In vivo, USP13 knockdown significantly inhibited tumor growth and lung metastasis. WISP1 overexpression in USP13-knockdown cells partially rescued these phenotypes, confirming the functional role of the USP13/WISP1 axis. Furthermore, knockdown of USP13 or WISP1 impaired the activation of the Wnt/CTNNB1 signaling pathway and reduced immune checkpoint marker expression, indicating a mechanism by which USP13 promotes immune evasion in ESCC. USP13 stabilizes WISP1 through deubiquitination, enhancing ESCC progression by activating the Wnt/CTNNB1 pathway and promoting immune evasion, making USP13 a potential therapeutic target in ESCC.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}