Background:Bladder cancer (BCA) shows significant prognostic differences between non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) forms. While NMIBC frequently recurs and can progress to invasive disease, reliable biomarkers to monitor this transition are lacking. Extracellular matrix (ECM) remodeling is a critical factor influencing tumor aggressiveness, yet the key regulators of ECM changes across BCA stages remain unclear. In this study, we investigate the role of COL1A2 in ECM-related tumor biology and its potential as a prognostic biomarker for BCA progression. Methods:We utilized a multi-step bioinformatics pipeline, analyzing RNA-seq data from TCGA and GEO datasets to identify molecular differences between NMIBC and MIBC. Prognostic markers were prioritized via differential expression analysis, Cox regression, and Kaplan-Meier survival analysis. The regulatory network was explored using protein-protein interaction analysis, and ECM-related activity was quantified through ssGSEA. Cell-type-specific insights were gained through single-cell RNA-seq analysis, and intercellular communication was deciphered using CellChat. Functional validation was performed through in vitro knockdown experiments in BCA cell lines. Results:COL1A2 emerged as a key prognostic ECM-related gene associated with MIBC. Single-cell RNA-seq analysis revealed that COL1A2 and ECM components were predominantly enriched in matrix cancer-associated fibroblasts (CAFs), with PTK2 (FAK, focal adhesion kinase) upregulated in epithelial cells undergoing epithelial-mesenchymal transition (EMT). CellChat analysis uncovered a dominant COL1A2-mediated signaling axis from matrix CAFs to EMT epithelial cells via COL1A1/2-SDC1/4 ligand-receptor interactions. Functional assays confirmed that COL1A2 knockdown significantly impaired MIBC cell invasion and migration by suppressing ECM remodeling and EMT. Conclusion:Our results suggest that the COL1A2-ECM-FAK signaling axis plays a critical role in MIBC progression, and COL1A2 could serve as a potential biomarker and therapeutic target for muscle-invasive bladder cancer.

High mobility group box 3 (HMGB3) acts as an essential participator in fundamental biological processes, including transcriptional regulation, chromatin remodeling and DNA repair. HMGB3 is highly expressed and functionally essential during embryonic development, particularly in the hematopoietic and nervous systems, but it is significantly downregulated or silenced in most normal adult tissues. Its aberrant upregulation has been revealed in numerous human malignancies, such as leukemia, as well as breast, bladder, colorectal and gastric cancer, and its expression levels have been established to be closely associated with poor prognosis of specific patients. Accordingly, the present review systematically explores the central roles of HMGB3 in mediating resistance to cancer therapy. This review focuses on its multifaceted mechanisms of maintaining cancer stemness, enhancing DNA damage repair, modulating cell death pathways and remodeling the tumor microenvironment, thereby contributing to the resistance to chemotherapy, radiotherapy, targeted therapy and immunotherapy collectively. HMGB3 can be accepted as a key target in the development of highly promising therapeutic strategies, given its pivotal involvement in multidrug resistance, which may offer novel avenues for overcoming clinical treatment resistance and improving patient outcomes.

Abstract Background Bladder cancer (BC) presents a major clinical challenge due to high recurrence and progression rates, highlighting the need for novel therapeutic targets. While the N6-methyladenosine (m6A) writer complex is broadly implicated, the specific function and regulatory mechanism of its adaptor protein RNA binding motif protein 15 (RBM15) remain poorly defined in BC. This study reveals the oncogenic role of RBM15 in BC and its m6A-dependent regulatory axis, providing a new rationale for targeted intervention. Methods The clinical relevance of RBM15 was established by assessing its expression and prognostic significance in public datasets and a large clinical cohort. The biological function of RBM15 and its effect on global m6A methylation were subsequently investigated using a comprehensive suite of in vitro assays and in vivo models. We performed integrated multiomics analyses (RNA-seq, m6A-seq, and RIP-seq) and validated the underlying molecular mechanisms by performing additional targeted assays to elucidate the downstream regulatory network. Finally, the therapeutic potential of targeting this axis was validated in preclinical models using the METTL3 catalytic inhibitor STM2457. Results RBM15 was significantly upregulated in BC, and its elevated expression served as an independent predictor of a poor prognosis. Functionally, RBM15 increased global m6A levels and promoted the malignant progression of BC cells both in vitro and in vivo; these oncogenic effects were reversed upon RBM15 knockdown. Mechanistically, RBM15 bound Zona Occludens 2 (ZO2) mRNA and recruited the methyltransferase 3–methyltransferase 14–Wilms’ tumor 1-associating protein (METTL3-METTL14-WTAP) methyltransferase complex to increase the level of the m6A modification on the ZO2 mRNA. This modification was recognized by YTH N(6)-methyladenosine RNA binding protein 2 (YTHDF2) to accelerate ZO2 mRNA decay. Although ZO2 expression was globally reduced, its preferential nuclear accumulation was increased, which promoted Snail expression and accelerated malignant progression. The METTL3 catalytic inhibitor STM2457 suppressed BC growth and lung metastasis by targeting the METTL3/RBM15/ZO2 axis, with no observable toxicity. Conclusions RBM15 acts as an oncogenic driver in BC by facilitating the m6A-dependent degradation of ZO2 mRNA via the recruitment of the METTL3 complex and recognition by YTHDF2. Targeting this METTL3/RBM15/ZO2 axis with STM2457 represents a promising therapeutic strategy for BC.

The clinical management of bladder cancer faces major challenges due to treatment resistance and recurrence, which require the development of new adjuvant strategies. The role of the gut microbiome in influencing bladder cancer progression and treatment response through the “gut-bladder axis” is gaining recognition. This understanding provides a theoretical rationale for exploring microbiota-targeting interventions, such as fecal microbiota transplantation (FMT). As a method capable of thoroughly reshaping the gut microbiota, FMT may have broad clinical potential. This review systematically explores the possible role of FMT in treating bladder cancer. It begins by summarizing the observational and causal evidence linking gut microbiota dysbiosis to bladder cancer, which forms the rationale for considering FMT as an intervention. Then, it discusses how FMT might improve therapeutic effectiveness, including regulation of microbial metabolites (such as short-chain fatty acids, tryptophan, and bile acids), repair of the intestinal barrier, induction of epigenetic reprogramming and modulation of the urinary microbiota. The review also considers potential scenarios for combining FMT with existing adjuvant therapies, including immunotherapy, chemotherapy, and radiotherapy. Finally, it objectively evaluates the key challenges in translating FMT into clinical practice, including effectiveness, safety, standardization, and regulatory or ethical issues, and outlines future directions. By synthesizing current evidence, this review highlights FMT as a potentially promising and innovative adjuvant strategy worthy of further investigation, which, if validated, could contribute to overcoming current therapeutic challenges in bladder cancer.

Digestive function significantly influences the bioavailability of iron in the diet, yet its impact on heme iron remains elucidated. We found that the bioavailability of orally administered myoglobin, a major provider of heme, is interfered with by amoxicillin. Concurrently, an excessive pork diet led to intestinal tissue damage and overexpression of Hmox1 in the small intestine of germ-free (GF) mice, but had minimal impact on ex-germ-free (ex-GF) mice, highlighting the role of gut microbiota in heme absorption and potential toxicity. Next-generation sequencing showed that dietary myoglobin and hemin affected the intestinal microbiota diversity, with Lactobacillus, Muribaculaceae and Bifidobacterium being enriched by myoglobin. Genetically, the enrichment of proteases and peptidases by myoglobin instead of hemin implied the regulated proteolytic capacity of the microbiota. The fluorescence resonance energy transfer system and peptidomics analysis revealed that microorganisms promote the full hydrolysis of myoglobin and subsequent heme release. We additionally confirmed that oligopeptides promote the internalization of heme through PEPT1 and endocytosis-dependent pathways. These findings elucidate the critical role of small intestinal microbiota in host digestion and provide new insights into the mechanism underlying the bioavailability of dietary myoglobin.

Prostate cancer (PCa) is a common malignancy in men, and bone metastasis is a leading cause of mortality in advanced-stage PCa. This study aims to identify critical genes involved in PCa bone metastasis, exploring biomarkers for prognosis and precision treatment. Forkhead Box Q1 (FOXQ1) was identified as a potential key gene through screening of public databases, and was found to be markedly upregulated in bone metastatic PCa compared to primary PCa. FOXQ1 promotes PCa cell proliferation and metastasis while inhibiting apoptosis. Additionally, FOXQ1 recruits macrophages, promotes M2 polarization, and enhances osteoclast differentiation in the tumor microenvironment. Mechanistically, FOXQ1 activates the transcription of Glycosyltransferase 8 Domain Containing 2 (GLT8D2) by directly binding to its promoter, and GLT8D2 upregulates the expression of C-C Motif Chemokine Ligand 2 (CCL2) by enhancing its N-glycosylation, thereby promoting PCa bone metastasis. Collectively, these findings establish FOXQ1 as a key regulator of PCa bone metastasis through the GLT8D2/CCL2 axis, and suggest that targeting this pathway may hold therapeutic promise for bone metastatic PCa.

Intratumoral microbes significantly influence tumor progression, yet their specific roles and host interactions in bladder cancer (BLCA) remain elusive. Integrating 16 S rRNA sequencing from an in-house cohort with TCGA data, we identified Methylobacterium as prominently enriched in adjacent non-tumor tissues and tightly correlated with host transcriptomic alterations. Through LASSO regression, we constructed and externally validated a Methylobacterium-associated four-gene prognostic signature (SLC1A6, BCHE, TXNRD1, CFL2). The model robustly stratified patient outcomes; high-risk patients exhibited significantly worse survival, characterized by an immunosuppressive microenvironment with elevated M2 macrophages, regulatory T cells, and higher TIDE scores indicating immune evasion. Crucially, in vitro experiments suggested that Methylobacterium supernatant exerted tumor-suppressive effects, profoundly inhibiting BLCA cell proliferation and colony formation while modulating host gene expression (downregulating BCHE and CFL2). Collectively, this study unveils the protective potential of intratumoral Methylobacterium and proposes a novel microbe-derived signature for predicting BLCA prognosis and immune status, providing new insights into microbiota-host crosstalk for future therapeutic strategies.

Postoperative recurrence is a major determinant of prognosis in bladder cancer. Early identification of patients at high risk is essential for optimizing individualized follow-up and therapeutic strategies. This study aimed to develop a comprehensive recurrence risk prediction model based on clinical characteristics, laboratory parameters, and postoperative follow-up data, and to identify the key risk factors associated with recurrence. A total of 488 patients with bladder cancer were retrospectively enrolled. Demographic, lifestyle, comorbidity, tumor-related, surgical, and laboratory data at 3 months postoperatively were collected. Univariate and multivariate analyses were conducted to identify recurrence-associated variables. Predictive models were constructed using four machine learning algorithms: eXtreme Gradient Boosting (XGBoost), Random Forest (RF), Support Vector Machine (SVM), and k-Nearest Neighbors (KNN). Model performance was evaluated using receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and k-fold cross-validation. Feature importance and individual risk contributions were interpreted using SHAP (SHapley Additive exPlanations) analysis. Age, smoking history, tumor stage, tumor number, tumor size, pathological grade, neutrophil-to-lymphocyte ratio (NLR), urine cytology, hematuria, NMP22, and alkaline phosphatase (ALP) were identified as independent predictors of bladder cancer recurrence. Among all models, XGBoost demonstrated the best predictive performance, with an AUC of 0.960 in the training set, 0.925 in the validation set, and 0.850 in the external validation cohort. SHAP analysis revealed that smoking history, tumor stage, tumor number, tumor size, pathological grade, NLR, urine cytology, hematuria, and NMP22 were the most influential predictors of recurrence and contributed significantly to inter-individual risk differences. The multidimensional machine learning–based recurrence prediction model developed in this study accurately identifies high-risk bladder cancer patients and elucidates key risk factors, offering a robust evidence base for personalized postoperative surveillance and intervention. Furthermore, it provides novel insights into the biological mechanisms underlying recurrence. Future studies with larger, multicenter cohorts are warranted to validate the model’s robustness and clinical applicability.

To examine the preliminary effects and feasibility of peer support on decision-making regarding fecal microbiota transplantation (FMT) among patients with recurrent urinary tract infections (rUTIs). This was a prospective, two-arm pilot study conducted from September 2023 to April 2024 in the urology outpatient departments of two tertiary hospitals in China using convenience sampling. Patients were assigned to either a peer support group or a control group. The intervention consisted of weekly WeChat-based interactions between trained peer supporters and patients for four weeks. Decision-making was assessed using validated tools including the Decisional Conflict Scale, Preparation for Decision Making Scale, Decision Self-Efficacy Scale, Choice Predisposition Scale, and Decisional Satisfaction Scale, all derived from the Ottawa Decision Support Framework. Anxiety and depression were measured using the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS). A total of 24 patients were assigned to a peer support group (n = 12) and a control group (n = 12). Compared with the control group, the peer support group showed higher FMT-related knowledge, stronger choice predisposition toward FMT, higher decision-making self-efficacy, and lower decisional conflict after the intervention. No significant between-group differences were observed in preparation for decision making, decisional satisfaction, anxiety, or depression. In this small exploratory pilot study, nurse-led peer support showed preliminary potential to improve selected decision-related outcomes among women with rUTIs considering FMT. Rather than confirming efficacy, this study supports the feasibility of a structured nurse-led peer support protocol and provides a basis for future larger-scale research. Given the small sample size, convenience sampling, and single cultural context, these findings should be interpreted cautiously and require confirmation in larger studies. Future studies should also assess whether these preliminary improvements are sustained and translate into actual treatment decisions and long-term decisional satisfaction.

Immunotherapy has achieved limited efficacy in prostate cancer (PCa), largely due to its profoundly immunosuppressive tumor microenvironment (TME). However, the metabolic mechanisms underpinning this immune resistance remain poorly defined. Here, we identify lactate dehydrogenase A (LDHA)-driven lactate metabolism as a critical regulator of myeloid-derived suppressor cell (MDSC) activation in PCa. Integrated metabolomic, single-cell, and spatial transcriptomic analyses revealed that LDHA is highly expressed in PCa malignant epithelial cells and correlates with increased lactate production and immune exclusion. LDHA-high tumors exhibited enriched infiltration of polymorphonuclear MDSCs (PMN-MDSCs), which were spatially co-localized with LDHA-positive tumor regions. Mechanistically, lactate uptake through monocarboxylate transporter 1 (MCT1) enhanced PMN-MDSC differentiation and upregulated Arg1 and NOS2, reinforcing T cell suppression. Genetic ablation of LDHA in murine models markedly reduced PMN-MDSC infiltration, restored CD8+T cell activity, and inhibited tumor growth. Pharmacological inhibition of LDHA with FX-11 synergized with anti-PD-L1 therapy, producing durable tumor regression. Collectively, these findings define LDHA-driven lactate metabolism as a key metabolic checkpoint in PCa immune evasion and provide a rationale for combining LDHA inhibition with immune checkpoint blockade to overcome immunotherapy resistance.

BACKGROUND:Docetaxel (DTX)-based therapy remains first-line treatment for advanced prostate cancer (PCa), yet its efficacy is often compromised by chemoresistance. Emerging evidence highlights that circular RNAs (circRNAs) contribute to the development of chemoresistance, but their specific functions in DTX-resistant PCa remain poorly understood. METHODS:By integrating molecular biology, cell biology, and immunology approaches, we investigated the mechanism by which hsa_circ_0003258 drives DTX resistance in PCa. RESULTS:We identified that hsa_circ_0003258 was significantly elevated in DTX-resistant patients of PCa. Functional experiments confirmed that hsa_circ_0003258 enhances DTX resistance both in vitro and in vivo by promoting cancer stem-like properties, independent of its linear transcript. Mechanistically, hsa_circ_0003258 directly bound the RRMs and KH1 domains of IGF2BP3 via its CAUU motif, augmenting the non-competitive interaction between IGF2BP3's KH4 domain and the 3'UTR of PSAT1 mRNA. This led to increased PSAT1 mRNA stability and activation of the serine biosynthesis, thereby reinforcing stemness and driving DTX resistance of PCa. To explore therapeutic potential, we engineered targeted nanoliposomes (HA-LNP@si-hsa_circ_0003258/cy7) which selectively accumulated in PCa xenografts and significantly inhibited tumor growth in combination with DTX. Co-treatment with Bix, a G9a inhibitor previously reported to suppress PSAT1 expression, further enhanced the antitumor efficacy of this combination, suggesting a potential synergistic therapeutic effect. CONCLUSION:Our findings reveal a novel hsa_circ_0003258/IGF2BP3/PSAT1 axis that enhances de novo serine synthesis and drives DTX resistance in PCa, highlighting this pathway as a promising therapeutic target.

Accurate cancer diagnosis is essential for fluorescence surgical navigation to eliminate tumors. Second near-infrared (NIR-II, 10 0 0-170 0 nm) probes with aggregation-induced emission (AIE) nature possess bright fluorescence in a biological environment. However, due to the large particle sizes, NIR-II AIE probes usually lead to high liver retention, which is not conducive to tumor enrichment. Therefore, this work constructs a novel amphiphilic NIR-II AIE molecule, TTB-PEG10 0 0, which can self-assemble into ultrasmall fluorescent dots (7 nm) in the aqueous environment with a maximum emission at 1080 nm. Based on its excellent photostability, morphological stability, and biocompatibility, TTB-PEG10 0 0 shows a desirable definition of angiography capability with high signal-to-background (SBR) in the NIR-II AIE window over 1300 nm. Notably, treatment with TTB-PEG10 0 0 in the glioma-tumor mice results in a significant enhancement of the accumulation in the tumor and reduction of the retention in the liver, in which the fluorescent ratio between tumor and liver (T/L) is 32-fold higher than that of their contrast (TTB-COOH NPs) prepared by the nanoprecipitation method. This work is the first report of an amphiphilic AIE molecule with NIR-II maximum emission and sub-10 nm size, which will promise for preclinical applications and inspire further exploration of NIR-II fluorophores for advanced biomedical imaging. (c) 2026 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of urological cancers. But immune-related adverse events (irAEs), especially high-grade irAEs, are a significant risk factor for survival and prognosis in this group of patients. As such, the ability to predict irAEs is of great interest. We retrospectively examined baseline blood tests, biochemical markers, and tumor expression of LCP1 and ADPGK in 112 patients with urological cancers who received either PD-1 or PD-L1 antibodies. LCP1 positivity, ADPGK positivity, and more significantly, the bivariate model of LCP1 and ADPGK positivity were highly predictive of irAEs after ICI treatment, with area under the curve (AUC) of 0.8415, 0.8759, and 0.9184, respectively. These models performed well across various cancer types, and the bivariate model was particularly more accurate in predicting ICI-induced irAEs in bladder cancer (BC), with an AUC of 0.9856. Our retrospective study suggests that LCP1 positivity, ADPGK positivity, and the bivariate model of LCP1 and ADPGK positivity may be valuable predictive markers for ICI-induced irAEs. These results may help guide more targeted and personalized ICI treatment for patients with urological cancers.

Purpose:Interstitial cystitis (IC) is a chronic inflammatory disease with autoimmune associations, particularly in ulcerative IC, a severe and refractory subtype. Oxidative stress plays a crucial role in IC pathogenesis, interacting with inflammation and immune cell infiltration. This study aimed to identify oxidative stress-linked biomarkers and explore their relationship with immune cell infiltration to enhance diagnosis and treatment strategies. Patients and Methods:The GSE711783 dataset from GEO was analyzed to identify differentially expressed genes in ulcerative IC. Oxidative stress-related genes were sourced from GeneCards, with hub genes identified via WGCNA and protein-protein interaction networks. Diagnostic markers were refined using machine learning, and a nomogram prediction model was developed. Diagnostic biomarkers were validated in vitro and in vivo, immune infiltration was assessed with CIBERSORT, and potential therapeutic drugs were identified through DSigDB. Results:Four diagnostic biomarkers-BMP2, MMP9, CCK, and NOS3-were identified and found to be associated with immune cells, including CD4+ T cells and eosinophils. Decitabine was identified as a potential therapeutic candidate. Experimental validation confirmed the expression of these biomarkers. Conclusion:This study identifies BMP2, MMP9, CCK, and NOS3 as key biomarkers, offering valuable insights into the diagnosis and treatment of IC.

Prostate cancer (PCa) is the second most common cancer in men worldwide. Protein arginine methyltransferase 7 (PRMT7) expression is associated with tumor growth, as it can drive tumor cell proliferation and promote its invasiveness in several types of cancer. However, its mechanism in PCa remains to be elucidated. In the present study, the function and associated mechanism of PRMT7 in PCa cells were investigated. The relationship between PRMT7 and PCa was analyzed using The Cancer Genome Atlas online database. Tissue chip techniques were used to identify the clinical relevance of PRMT7 expression. PRMT7 expression levels in PCa tissues and cells were verified using reverse transcription-quantitative PCR (RT-qPCR). Cell cycle, migration, proliferation and apoptosis of PC3 and DU145 cells were observed using flow cytometry, Cell Counting Kit-8, wound healing, plate cloning and cell invasion assays. Gene set enrichment analysis and chip expression profiles were used to predict the potential signaling pathway involved in the action of PRMT7 in PCa. First, The Cancer Genome Atlas database, tissue microarray analysis and RT-qPCR revealed that PRMT7 expression was increased in PCa tissues and cells. Furthermore, small interfering RNA-mediated PRMT7 knockdown led to a notable reduction in the proliferation of cells, increased apoptosis, affected the cell cycle and decreased cell migration and invasion. Furthermore, PRMT7 regulated the functions of Yin Yang 1 (YY1), tumor protein p53 (TP53), cyclin D2 (CCND2), CDK6 and retinoblastoma 1 (RB1) in PCa. PRMT7 may promote proliferation, migration and metastasis in PCa cells by regulating the activity of YY1, TP53, CCND2, CDK6 and RB1 in the cell cycle signaling pathway.

Background:Due to the specific nature of uncomplicated urinary tract infections (uUTIs), female patients are often labelled with stigma. The presence of stigma has a serious impact on their mental health, social functioning and healthcare-seeking behavior, which in turn affects disease recovery. Purpose:To identify the sense of stigma and its associated influencing factors in female patients with uUTIs. Patients and Methods:A cross-sectional study was conducted between December 2022 and December 2023, during which samples were collected from 240 adult women with uUTIs from various healthcare facilities in Wuxi, China. General information questionnaires, the Chinese Version of the Social Impact Scale (range 24 to 96), the Multidimensional Perceived Social Support Scale, the Self-Rated Anxiety Scale and the Self-Rated Depression Scale were used. SPSS 27.0 was used to create the database and statistical analysis was performed after data entry by two people. Results:A total of 240 validated questionnaires were collected in this study, and the patients' stigma score was 2.71 ± 0.37 (at a moderate level of stigma). Internalized stigma was the highest and social isolation the lowest of the four dimensions of stigma. Multiple linear regression analyses showed that the level of stigma was higher in patients with symptoms of urinary frequency, urgency, and hematuria uUTIs. uUTIs with longer duration of symptoms, more frequent episodes, less knowledge about the disease, higher anxiety and depression, and lower levels of perceived social support for the disease had higher levels of stigma. Conclusion:Studies have shown that female patients with uUTIs have a moderate level of stigma. Nursing administrators should pay attention to the sense of shame in this population and enhance health promotion to reduce their sense of stigma.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating condition characterized by pelvic pain and urinary urgency and frequency with an unclear etiology. Emerging evidence implicates microbiome dysbiosis-disruptions in the microbial communities inhabiting the body-in IC/BPS pathophysiology. This review synthesizes the literature on microbial alterations in IC/BPS, including urinary, vaginal, and gastrointestinal microbiota, and their interactions with host inflammatory and metabolic pathways. PATIENT SUMMARY: We reviewed studies from the past 10 years on microbial communities in the body for patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Studies have revealed significant changes in microbial species for these patients, especially in urine. However, research on whether IC/BPS can be treated with interventions to modify microbial communities in the body is still needed.

Equol, a naturally occurring phytoestrogen derived from the fermentation of soy and soy-based products by gut bacteria, is recognized for its diverse health benefits. While there is speculation about its association with cancer prevention, the scientific community has yet to reach a consensus due to the variability in research findings. Our study aims to shed light on this topic by examining the correlation between urine equol concentrations and the cancer risk among the American population. The National Health and Nutrition Examination Survey (NHANES) is a national survey of U.S. civilians in which cancer participants are enrolled in a database by a sample questionnaire. This study included 2797 Americans aged 40 years and older in the NHANES database (2005–2010). The relationship between urine equol concentration and cancer was analysed using weighted logistic regression models, stratified analysis, smoothed curve fitting and threshold effect analysis were also performed. Among the 2797 participants in our study, 390 individuals received a cancer diagnosis. Our findings indicate a positive correlation between urine equol levels and the risk of cancer. Notably, individuals in the highest quartile of equol excretion exhibited a significantly elevated risk of cancer, with a 25.4% increase compared to those in the lowest quartile (POR = 1.254, 95% CI: 1.252, 1.256), after fully adjusting for confounders. Similar results were observed in other adjusted models. A non-linear relationship in the shape of an inverted U-shape can be observed by smoothed curve fitting, and the inflection point is 25.5. Urinary equol concentrations below 25.5 ng/ml were positively associated with cancer risk, while equol concentrations above 25.5 ng/ml showed a slight negative trend in cancer risk. However, further prospective studies are needed to provide more robust evidence and confirmed in large clinical trials.

Previous studies have identified that lens epithelium-derived growth factor (LEDGF) interacts with SETD2-dependent histone H3 trimethylated at lysine 36 (H3K36me3) to mediate transcriptional elongation. However, the original LEDGF recognition H3K36me3 epigenetic regulatory axis no longer exists in SETD2 mutant clear cell renal cell carcinoma (ccRCC) patients, and a new transcription system needs to be discovered. In this study, the authors demonstrated the novel interaction between LEDGF and H3R17me2a. In detail, Asn38 and Asp57 of LEDGF Proline-Tryptophan-Tryptophan-Proline (PWWP) domain are the key binding sites validated by peptide pull-down assays. Subsequently, a series of in vitro and in vivo experiments showed that PPAT, PAICS, GART, ADSL, and ADSS2 are key target genes. Collectively, LEDGF binds H3R17me2a to regulate purine nucleotide metabolism in SETD2 mutant ccRCC cells, promoting tumor proliferation, and may be an effective therapeutic target.

Purpose:Long noncoding RNAs (lncRNAs) are increasingly being recognized to play important roles in cancer pathogenesis. However, the functional mechanisms of most lncRNAs remain poorly understood. Materials and Methods:RNA sequencing was performed to identify differentially expressed lncRNAs between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). In vitro and in vivo assays were conducted to investigate the functional role of lncRNA deoxyguanosine kinase 1 antisense RNA 1 (DGUOK-AS1). Meanwhile, RNA pull-down, RNA immunoprecipitation, co-immunoprecipitation, Western blot, and reverse transcription quantitative polymerase chain reaction assays were performed to explore the potential regulatory mechanisms of DGUOK-AS1 on its target genes. Results:Our analysis revealed a significant upregulation of lncRNA DGUOK-AS1 in MIBC compared with NMIBC. Functionally, DGUOK-AS1 was found to enhance the proliferation and invasion of bladder cancer (BC) cells by interacting with elongation factor Tu GTP binding domain containing 2 (EFTUD2), a 116-kDa U5 small nuclear ribonucleoprotein component. Mechanistically, DGUOK-AS1 directly binds to EFTUD2 and the deubiquitinating protein valosin-containing protein-interacting protein 1, thereby shielding EFTUD2 from ubiquitination and subsequent degradation. Furthermore, EFTUD2 orchestrates the exclusion of cassette exon 11 from macrophage-stimulating 1 receptor, leading to the production of the RON∆165 isoform. This isoform activates the Akt/PKB signaling pathway, which is crucial for cancer progression. Conclusion:DGUOK-AS1 drives BC progression via the EFTUD2/MST1R/Akt axis, offering a promising therapeutic target for BC treatment.