Journal of Cancer最新文献

{"title":"LncRNA HOXB-AS4 Promotes Tumor Malignant Phenotype in Head and Neck Squamous Cell Carcinoma and Serves as a Prognosis Marker.","authors":"Shanshan Lv, Jie Guo, Lin Du, Yanwei Luo, Hao Tian, Yan Liu","doi":"10.7150/jca.111037","DOIUrl":"https://doi.org/10.7150/jca.111037","url":null,"abstract":"<p><p><b>Background:</b> Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumor in the head and neck with a high suicide rate. Numerous studies have indicated that lncRNAs play a significant role in tumor occurrence and development, and that they may serve as promising diagnostic markers and therapeutic targets. The lncRNA HOXB-AS4 is substantially expressed in HNSCC; this work aimed to clarify the role of HOXB-AS4 in HNSCC and to further investigate its potential mode of action. <b>Methods:</b> In this study, bioinformatics analysis was utilized to identify differentially expressed lncRNAs from RNA-seq data in the TCGA-HNSCC data set. The effect of lncRNA on HNSCC cell function was assessed using cell function tests. The probable downstream target mRNA of lncRNA was discovered after analyzing the differential mRNA and reviewing the literature. Mass spectrometry was utilized to investigate the signaling pathways it may control. RT-qPCR and western blotting were employed to confirm its regulatory action. <b>Results:</b> HOXB-AS4 was abnormally overexpressed in HNSCC, which was related with poor clinical characteristics and prognosis, as well as promoting HNSCC cell migration, invasion, proliferation, and clone formation. The elevated expression of HOXB-AS4 in HNSCC may play a role in tumor promotion by influencing the HOXB7 gene located on the same chromosome, thereby activating the phosphorylation of AKT. <b>Conclusions:</b> HOXB-AS4 may promote malignancy in HNSCC by controlling the HOXB7/AKT pathway.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 9","pages":"2997-3014"},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12244335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Predictive Value of the Cholesterol-to-Natural Killer Cell Ratio in Colorectal Cancer.","authors":"Qian-Qian Liu, Yan Chen, Zhi-Qing Zhan, Hao-Lian Wang, Ying-Xuan Chen","doi":"10.7150/jca.114813","DOIUrl":"https://doi.org/10.7150/jca.114813","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; We constructed a novel biomarker cholesterol (C)-to-natural killer (NK) cell ratio (CNR) to reflect the synergistic effect of cholesterol metabolism and inflammation on colorectal cancer (CRC) outcomes. This study aimed to investigate the clinical significance and predictive value of CNR in CRC and develop a simple and reliable prognostic model for predicting OS in CRC patients. &lt;b&gt;Methods:&lt;/b&gt; We retrospectively collected the hematology data and medical records of 213 patients with CRC at Renji hospital and the histological data and medical records of 94 patients with CRC included in a tissue microarray. The association between tumor biomarkers and survival was evaluated using the log-rank test. The diagnostic efficacy of CNR was assessed using receiver operating characteristic curves. The overall survival (OS) rates were estimated using the Kaplan-Meier method. Cox proportional hazards regression was employed in both univariate and multivariate analyses to identify independent prognostic factors, which were subsequently utilized to develop a predictive model for OS. The performance of the model was evaluated using the concordance index (C-index) and calibration plots. The patients were stratified based on the total risk scores calculated from the model. The differences in OS among these groups were assessed using the Kaplan-Meier method. The relationship between cholesterol and NK cells was analyzed by investigating the colon cancer datasets TCGA and GSE39582. &lt;b&gt;Results:&lt;/b&gt; The TNM stage III-IV CRC group had significantly higher blood levels of cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), CNR, and carcinoembryonic antigen (CEA), and shorter progression-free survival (PFS) than the TNM stage I-II CRC group (all, &lt;i&gt;P&lt;/i&gt; &lt; 0.05). The blood CNR correlated negatively with PFS (&lt;i&gt;P&lt;/i&gt; &lt; 0.001). Elevated tissue CNR levels were an independent risk factor for CRC, where low-tissue CNR patients demonstrated significantly prolonged survival (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). The area under the curve for blood CNR was 0.743. The multivariate analyses indicated that tumor location (&lt;i&gt;P&lt;/i&gt; = 0.004), TNM stage (&lt;i&gt;P&lt;/i&gt; = 0.004), and tissue CNR (&lt;i&gt;P&lt;/i&gt; = 0.033) were independent prognostic factors of OS in CRC. The nomogram model was based on these variables and demonstrated good calibration and predictive performance, achieving an excellent C-index of 0.737 [95% confidence interval (CI), 0.674-0.779]. The expression of the key cholesterol biosynthesis players &lt;i&gt;HMGCR&lt;/i&gt;, &lt;i&gt;SQLE&lt;/i&gt;, and &lt;i&gt;SREBP2&lt;/i&gt; was not significantly associated with NK cell-mediated cytotoxicity-related gene signatures. &lt;i&gt;HMGCR&lt;/i&gt; and &lt;i&gt;SQLE&lt;/i&gt; were negatively associated with &lt;i&gt;CD56&lt;/i&gt;, a phenotypic NK cell marker (&lt;i&gt;P&lt;/i&gt; &lt; 0.001). &lt;b&gt;Conclusion:&lt;/b&gt; This is the first study to explore the predictive value of CNR in CRC, which was a promising predictor of CRC progression. The developed nomogram model may serve as a reliable tool for p","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 9","pages":"2946-2958"},"PeriodicalIF":3.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12244336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radioresistant triple-negative breast cancer cells release β-catenin containing extracellular vesicles to promote cancer stem cell activity of bystanders.","authors":"Yueh-Chun Lee, Peng-Ju Chien, Yu-Ting Chang, Yu-Hao Huang, Chin-Fang Chang, Shao-Ti Li, Wen-Wei Chang","doi":"10.7150/jca.111555","DOIUrl":"https://doi.org/10.7150/jca.111555","url":null,"abstract":"<p><p><b>Background:</b> Triple-negative breast cancer (TNBC) frequently develops radioresistance, yet the mechanisms remain incompletely elucidated. This study is the first to investigate how β-catenin, transported by extracellular vesicles (EVs) from radioresistant TNBC cells, promotes radioresistance and enhances cancer stem cell (CSC) activity in recipient TNBC cells, offering a novel mechanism distinct from prior EV-related findings in other cancers. <b>Methods and Results:</b> A radioresistant cell line (231-RR) was developed from MDA-MB-231 cells, and EVs were isolated for characterization. EVs from 231-RR cells decreased radiosensitivity in parental MDA-MB-231 and two other TNBC cell lines (MDA-MB-468 and Hs578T), as shown by clonogenic assay. These EVs also enhanced CSC activity in MDA-MB-231 and Hs578T cells, demonstrated through primary and secondary mammosphere formation. The effects were nullified when using EVs from 231-RR cells treated with the EV secretion inhibitor GW4869. 231-RR-derived EVs showed elevated β-catenin levels and increased active β-catenin and stemness proteins (c-Myc, OCT4, SOX2) in recipient TNBC cells. The β-catenin inhibitor CCT-031374 prevented EV-mediated enhancement of radioresistance and CSC activity. Public data analysis from breast cancer patients revealed post-radiotherapy upregulation of the β-catenin pathway, with elevated <i>CTNNB1</i>, <i>MYC</i>, and <i>CD44</i> expression, alongside reduced <i>CDKN2A</i> and <i>CDH1</i> levels, supporting clinical relevance. <b>Conclusions:</b> This study uniquely demonstrates that EVs from radioresistant TNBC cells transfer β-catenin to confer radioresistance and enhance CSC activity in recipient cells, a mechanism not previously reported in TNBC. These findings suggest the potential of EV-β-catenin derived as a novel biomarker for predicting radiotherapy outcomes and recurrence risk in TNBC patients, pending development of sensitive detection methods.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 9","pages":"2890-2902"},"PeriodicalIF":3.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12243990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alternative splicing factor RAB3IP as a novel risk signature to predict the prognosis of colorectal cancer.","authors":"Zhengwei Zhou, Fei Gao, Han Lei, Haixuan Wen, Jiaxi Tang, Yulong Peng, Lili Fan, Lu Xu, Guang Shu","doi":"10.7150/jca.110271","DOIUrl":"https://doi.org/10.7150/jca.110271","url":null,"abstract":"<p><p>Emerging evidence suggests that aberrant alternative splicing plays a vital role in the development of tumors. However, the expression of splicing factors (SF) in colorectal cancer and its relationship with prognosis is still unclear. Here, we divided patients into high-risk and low-risk groups through univariate COX analysis and LASSO regression analysis, and selected 13 alternative splicing factors that are highly correlated with prognosis for subsequent analysis. We systematically analyzed the prognostic value of transcription levels of SFs in colorectal cancer (CRC) and found that RAB3A interacting protein (RAB3IP), programmed cell death 4 (PDCD4), golgin B1 (GOLGB1), and neuregulin 4 (NRG4) as the most predictive markers for the prognosis of CRC. After comparing the expression of four splicing factors in cancer tissues with normal tissues as well as OS analysis, it is strongly indicated that only RAB3IP demonstrates a significant positive correlation with favorable prognosis. Accordingly, we established a risk signature of transcription levels of RAB3IP as an independent prognostic marker for CRC. Moreover, by the Gene Set Enrichment Analysis (GSEA), we demonstrated that the RAB3IP was correlated to Cell Cycle, WNT pathway and Spliceosome in cancer. In conclusion, our findings demonstrate that SFs play a critical role in CRC pathogenesis, and identify RAB3IP as a novel prognostic biomarker for CRC.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 9","pages":"2959-2969"},"PeriodicalIF":3.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12244333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PARK7 is a Key Regulator of Oxidative Stress - Related Breast Cancer Risk: A Multi-Omics Study.","authors":"Tianhua Wang, Yan Yao, Minpu Zhang, Hao Luan, Xinjie Chang, Lijuan Liu, Changgang Sun","doi":"10.7150/jca.111796","DOIUrl":"https://doi.org/10.7150/jca.111796","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Oxidative stress (OS) is closely associated with the occurrence and progression of breast cancer (BC). However, its role as a potential etiological factor or trigger remains unclear. This study aims to systematically investigate the potential causal effects and mechanisms of OS-related genes in BC by integrating multi-omics data. &lt;b&gt;Methods:&lt;/b&gt; This study obtained summary data for blood methylation (mQTL), gene expression (eQTL), alternative splicing (sQTL), and protein abundance (pQTL) from their respective quantitative trait loci (QTL) studies. The genetic association data for breast cancer (BC) were primarily derived from the Breast Cancer Association Consortium (BCAC) and were validated using the UK Biobank (UKB) and FinnGen databases. SMR (Summary-data-based Mendelian Randomization) analysis was performed to evaluate the associations between the molecular characteristics of oxidative stress-related genes and BC. Subsequently, colocalization analysis was conducted to determine whether the identified signals share the same causal genetic variants. Whole-transcriptome association studies (TWAS), whole-proteome association studies (PWAS), and multi-marker analysis with genomic annotation (MAGMA) were used as sensitivity analyses. In addition, the significant genes were validated using multi-omics analysis of blood samples in an independent cohort from Weifang Traditional Chinese Medicine Hospital. &lt;b&gt;Results:&lt;/b&gt; By integrating multi-omics data from mQTL, eQTL, sQTL, and pQTL analyses, we identified PARK7 as a key oxidative stress-related gene that showed significant associations with breast cancer (BC) at multiple levels. Elevated gene expression of PARK7 (pSMR = 5.79E-06, OR = 0.91) and protein levels (pSMR = 8.46E-06, OR = 0.83) were significantly associated with reduced BC risk. In the mQTL analysis, cg10385390 (pSMR = 2.03E-03, OR = 1.09) and cg11518359 (pSMR = 3.54E-03, OR = 0.88) were significantly associated with BC. In the sQTL analysis, PARK7 (chr1:7961793-7962763) (pSMR = 8.87E-06, OR = 1.03) and PARK7 (chr1:7961735-7962763) (pSMR = 9.38E-06, OR = 0.97) were significantly associated with BC. In the integrated mQTL-eQTL SMR analysis, cg10385390 (pSMR = 7.61E-15, OR = 0.47) and cg11518359 (pSMR = 4.56E-09, OR = 2.78) exhibited significant associations. In the integrated sQTL-pQTL SMR analysis, PARK7 (chr1:7961793-7962763) (pSMR = 4.62E-44, OR = 0.85) and PARK7 (chr1:7961735-7962763) (pSMR = 6.56E-42, OR = 1.19) both showed significant associations. These findings revealed the multidimensional molecular mechanisms by which PARK7 regulates breast cancer risk through the oxidative stress pathway. All findings were supported by colocalization analysis (PPH4 &gt; 0.7). Validation in an independent population cohort indicated that plasma levels of PARK7 mRNA and protein in breast cancer patients were significantly lower than those in healthy controls, consistent with the aforementioned results. &lt;b&gt;Conclusion:&lt;/b&gt; This s","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 9","pages":"2877-2889"},"PeriodicalIF":3.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12244032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ESCO2 promotes the proliferation of hepatocellular carcinoma through the PI3K/AKT/ mTOR signaling pathway.","authors":"Dapeng Chen, Yue Huang, Weixin Zhang, Youcheng Zhang, Yi Bai, Yamin Zhang","doi":"10.7150/jca.112087","DOIUrl":"https://doi.org/10.7150/jca.112087","url":null,"abstract":"<p><p><b>Background:</b> Establishment of sister chromatid cohesion N-Acetyltransferase 2 (<i>ESCO2</i>) is a gene implicated in the establishment of sister chromatid cohesion (SCC) and cell proliferation. We aimed to explore how <i>ESCO2</i> affects the proliferation of hepatocellular carcinoma (HCC). <b>Methods:</b> We analyzed ESCO2 expression levels and their association with clinical prognosis using the TCGA, HCCDB, and ICGC databases. Bioinformatics methods were employed to investigate potential regulatory pathways involving ESCO2. CCK-8 assays, colony formation assays, and flow cytometry were used to examine the impact of <i>ESCO2</i> knockdown on the malignant biological behavior of HCC cells. Western blotting was utilized to identify the specific regulatory mechanism of ESCO2. <b>Results:</b> <i>ESCO2</i> was significantly upregulated in HCC tissues and correlated with a worse prognosis. Bioinformatics analysis revealed that <i>ESCO2</i> regulated pathways related to the cell cycle and cell proliferation. Furthermore, knockdown of <i>ESCO2</i> significantly inhibited HCC cell proliferation both <i>in vivo</i> and <i>in vitro</i>. Most importantly, <i>ESCO2</i> stimulated the PI3K/AKT/mTOR pathway, which ultimately accelerated the cell cycle and inhibited apoptosis, promoting HCC progression. <b>Conclusion:</b> The present study elucidated the mechanism by which <i>ESCO2</i> regulates HCC proliferation: <i>ESCO2</i> promotes HCC proliferation by accelerating the cell cycle and inhibiting apoptosis via the PI3K/AKT/mTOR signaling pathway.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 9","pages":"2929-2945"},"PeriodicalIF":3.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12244334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ITM2A as a potential prognostic marker for triple-negative breast cancer.","authors":"Can Jiang, Ruixin Feng, Yongqian Zhao, Jingting Zhang, Na Han, Yuzhu Zhang, Guang Shu, Gang Yin, Maonan Wang","doi":"10.7150/jca.114801","DOIUrl":"https://doi.org/10.7150/jca.114801","url":null,"abstract":"<p><p>Different subtypes of breast cancer pose great challenges for precision therapy, especially triple-negative breast cancer (TNBC), because it lacks effective therapeutic targets and is highly resistant to chemotherapy. In this study, the transmembrane protein ITM2A was systematically identified as a novel prognostic biomarker and potential therapeutic target for TNBC. ITM2A was found to be significantly under expressed in TNBC tissues, as revealed by differential expression profiling. Furthermore, patients exhibiting low ITM2A expression demonstrated worse overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS). A combined multi-omics analysis revealed a significant association between low ITM2A expression and immunosuppressive microenvironmental features. It is noteworthy that the ITM2A high-expression group exhibited substantial clinical benefits in anti-PD-L1 treatment (AUC=0.982) and CAR-T treatment (AUC=0.827). Gene Ontology functional annotation and KEGG pathway enrichment analysis indicated that ITM2A may coordinate anti-tumor immune responses by regulating copper ion metabolic reprogramming and immune checkpoint networks. Pharmacogenomic analysis further confirmed that the expression level of ITM2A was negatively correlated with the sensitivity of etoposide. By establishing the 'immunometabolism-therapeutic response' regulatory axis of ITM2A, this study hopes to provide an innovative theoretical basis for the targeted treatment of TNBC and the precise stratification of immunotherapy.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 9","pages":"2903-2916"},"PeriodicalIF":3.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12244017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRABP2 promotes metastasis and lipid droplet accumulation in non-small cell lung cancer by downregulating PLAAT4.","authors":"Jie Xia, Bi Peng, Jianhua Wang, Fang Li, Guoxian Long","doi":"10.7150/jca.112019","DOIUrl":"https://doi.org/10.7150/jca.112019","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) is a highly prevalent and aggressive cancer with a high incidence. While cellular retinoic acid binding protein 2 (CRABP2) has been implicated in tumor progression, metastasis and drug resistanceacross multiple cancer types, its functional role and molecular mechanisms of CRABP2 in NSCLC progression remain largely unexplored. In this study, we demonstrated that CRABP2 expression was significantly elevated in NSCLC tissues compared to adjacent normal tissues, and high levels of CRABP2 correlated with reduced overall survival. Functionally, knockdown of CRABP2 inhibited NSCLC cell proliferation, migration, and invasion, and lipid droplet accumulation <i>in vitro</i>, while CRABP2 targeting inhibited tumor growth, lipid droplet content and metastasis in xenograft model. Mechanistically, CRABP2 was identified to bind to Phospholipase A/acyltransferase 4 (PLAAT4) and decreases its protein stability. Notably, inhibition of PLAAT4 reverses the shCRABP2-induced suppression of malignant phenotypes and lipid droplet formation. our findings reveal a novel CRABP2/PLAAT4-mediated lipid metabolic axis drives NSCLC progression and metastasis. These findings suggest that targeting CRAPB may offer a novel approach to therapeutic intervention for NSCLC.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 9","pages":"2917-2928"},"PeriodicalIF":3.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12244087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Periplocin Targets HDAC10 to Inhibit NF-κB Signaling and Induce Apoptosis in Myeloid Leukemia Cells.","authors":"Wenjie Li, Shuping Lai, Jingxian Chen, Ziang Chen, Yanying Zhou, Rongfang Wei, Yan Chen","doi":"10.7150/jca.113591","DOIUrl":"https://doi.org/10.7150/jca.113591","url":null,"abstract":"<p><p><b>Background</b>: Periplocin, a bioactive compound extracted from <i>Cortex periplocae</i>, has long been employed in traditional medicine for its diverse therapeutic effects, particularly in alleviating inflammation and inhibiting cancer progression. However, despite its potential benefits, the underlying molecular mechanisms of periplocin, especially in the context of leukemia treatment, remain poorly elucidated, warranting further investigation to uncover its precise role and therapeutic targets. <b>Methods</b>: A comprehensive approach combining network pharmacology and transcriptomic analysis was utilized to identify HDAC10 as a critical downstream target of periplocin. Molecular docking and dynamic simulation studies were performed to elucidate the interaction between periplocin and HDAC10 at the molecular level. Additionally, functional assays, including apoptosis induction, cell cycle regulation, and pathway inhibition experiments, were conducted to validate the mechanistic role of HDAC10 and its relevance to periplocin's anti-leukemic effects. <b>Results</b>: Periplocin was identified as an effective inhibitor of HDAC10, binding specifically to its hydrophobic active pocket and suppressing its enzymatic activity. This inhibition disrupted downstream signaling, particularly the NF-κB pathway, leading to significant apoptosis and cell cycle arrest in leukemia cells. These results therapy, offering insights into its mechanism of action through HDAC10 targeting. <b>Conclusion</b>: In conclusion, periplocin, as a novel natural compound, exhibits significant anti-leukemia activity, highlighting its potential as a promising therapeutic candidate for leukemia treatment. The findings contribute to the growing interest in natural compounds as innovative solutions for addressing unmet clinical needs in hematological malignancies.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 9","pages":"2970-2983"},"PeriodicalIF":3.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12244337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Multi-Omics Analysis and Experimental Validation Identify SPOP as a Prognostic Biomarker and Immune Regulator in Lung Adenocarcinoma.","authors":"Yu Wang, Tao Jiang, Ziyou Lin, Peijun Dai, Wenxin Wei, Chengyuan Dong, Xuelin Zhang, Zhifeng Zhang","doi":"10.7150/jca.111751","DOIUrl":"https://doi.org/10.7150/jca.111751","url":null,"abstract":"<p><p><b>Background:</b> The speckle-type POZ protein (SPOP) has emerged as an important regulator of protein degradation in various cancers. However, the precise role of SPOP in lung adenocarcinoma (LUAD) remains unclear, particularly in relation to its expression patterns, prognostic significance, and potential as a therapeutic target. This study aimed to investigate the expression, prognostic value, and biological functions of SPOP in LUAD, and to explore its potential as a biomarker for personalized treatment strategies. <b>Methods:</b> We performed a comprehensive analysis of SPOP expression using multiple public datasets, including TCGA, TCGA-GTEx, and GEO. Survival analyses were conducted through Cox regression and Kaplan-Meier methods to assess the prognostic significance of SPOP in LUAD. Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA) were employed to uncover biological pathways associated with SPOP expression. Immune microenvironment analysis and drug sensitivity data from the GDSC database were used to explore the potential role of SPOP in immune modulation and therapeutic response. The biological role of SPOP in LUAD was further explored through molecular docking analysis and experimental validation. <b>Results:</b> SPOP expression was significantly reduced in LUAD compared to normal tissues, with lower expression correlating with poor overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). Cox regression analysis confirmed that SPOP is an independent prognostic factor for LUAD. Functional analyses revealed that low SPOP expression was associated with disrupted immune regulation and altered metabolic pathways, potentially driving tumor progression. Immune profiling identified significant correlations between SPOP expression and immune cell recruitment, inflammatory signaling, and LUAD subtypes. Drug sensitivity analysis suggested that low SPOP expression is linked to increased sensitivity to zibotentan and 5-fluorouracil. Additionally, molecular docking analysis revealed key interaction sites between SPOP and NANOG, and SPOP knockdown in A549 and T24 cells resulted in downregulation of immune markers CD47 and CD155. <b>Conclusion:</b> SPOP is a reliable independent prognostic biomarker in LUAD, influencing tumor progression, immune microenvironment, and therapeutic response. Our findings support the potential of SPOP as a novel therapeutic target for personalized treatment strategies in LUAD.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 9","pages":"2984-2996"},"PeriodicalIF":3.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12244332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}