Esophageal squamous cell carcinoma (ESCC) remains a highly lethal malignancy, and the molecular drivers of its progression are not fully defined. Dickkopf-3 (DKK3), a context-dependent modulator of oncogenic signaling, has been implicated in several solid tumors, but its role in ESCC is unclear.

Bladder cancer remains a significant clinical challenge due to high recurrence and progression rates, necessitating novel therapeutic strategies. Oncolytic viruses, such as the herpes simplex virus type 2-based OHSV2, have demonstrated promising antitumor effects through direct oncolysis and immune activation. This study investigated the efficacy, safety, and molecular mechanisms of OHSV2 in the treatment of bladder cancer. In vitro and in vivo experiments demonstrated that OHSV2 potently inhibited bladder cancer cell proliferation, migration, and clonogenicity in a dose-dependent manner, while exhibiting a favorable safety profile. Critically, OHSV2 treatment triggered a pro-inflammatory tumor immune microenvironment, characterized by increased infiltration and activation of CD8+ T cells. Mechanistically, OHSV2 induced pyroptosis in bladder cancer cells via the canonical Caspase-1/Gasdermin D (GSDMD) pathway, accompanied by increased interleukin-18 (IL-18), interleukin-1β (IL-1β), and lactate dehydrogenase (LDH) release. Further analysis identified NOD-like receptor family pyrin domain containing 3 (NLRP3) as the key upstream pattern recognition receptor for Caspase-1/GSDMD activation, and Toll-like receptor 4 (TLR4) as a critical mediator of NLRP3-dependent pyroptosis. Inhibition of TLR4 or NLRP3 partially reversed OHSV2-induced cytotoxicity, confirming their functional roles. Additionally, combining OHSV2 with the TLR4 agonist enhanced pyroptosis in a subcutaneous xenograft model, amplified antitumor immunity, and improved tumor control in vivo, suggesting potential synergism for clinical translation. These findings elucidate a novel TLR4/NLRP3/Caspase-1/GSDMD axis as the core mechanism behind the antitumor effect of OHSV2 and propose a rationale for its combination with immunomodulators to improve outcomes in bladder cancer.

Cancer and its treatments often lead to inflammation, muscle problems, and ongoing loss of physical function, as reflected by alterations in circulating microRNAs (miRNAs). In this study, we measured levels of selected muscle- (miR-1, miR-133, miR-208, miR-486, and miR-499) and inflammation-related (miR-21, miR-126, miR-146, and miR-155) miRNAs in breast cancer patients and aimed to explore, using stratified analyses, how their levels relate to cancer subtype, treatment modality, treatment timing, and age.

Simpson-Golabi-Behmel syndrome (SGBS) is an overgrowth syndrome associated with an increased risk of certain malignancies; however, gliomas have not previously been reported in patients with SGBS. Loss-of-function variants in glypican-3 (GPC3) represent the primary molecular mechanism underlying SGBS-related overgrowth and tumorigenesis, although their relationship with gliomas remains unclear. We report a case of an 18-year-old male who had been clinically diagnosed with Sotos syndrome in childhood. He presented with sudden impaired consciousness, and neuroimaging revealed a large tumor in the left occipitoparietal lobe, which was subsequently resected. Histopathological analysis demonstrated a pediatric-type diffuse hemispheric glioma, H3 G34-mutant (CNS WHO grade 4). Next-generation sequencing of peripheral blood DNA identified a germline hemizygous deletion encompassing exons 3-5 of GPC3, leading to a revised diagnosis of SGBS. To our knowledge, this is the first reported case of SGBS associated with a glioma. This case raises the possibility that GPC3 alterations may contribute to gliomagenesis, including in H3 G34-mutant diffuse hemispheric glioma.

Metabolic reprogramming, particularly the altered nucleotide metabolism, is a critical driver of tumor heterogeneity and malignant progression in gastric cancer (GC). However, the core molecular determinants orchestrating this metabolic shift and its subsequent impact on the tumor microenvironment (TME) remain elusive. We integrated single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and bulk RNA-seq data to delineate the metabolic landscape of GC. The metabolic vulnerabilities and functional roles of the identified hub gene were systematically validated using in vitro assays, in vivo xenograft models, and pharmacological metabolic interventions. Pathway-level metabolic flux inference via scRNA-seq revealed a pronounced shift toward nucleotide interconversion and pyrimidine synthesis in malignant epithelial cells. We identified GNAS as a key metabolic hub gene, which is consistently upregulated in highly malignant subsets and strongly predictive of poor patient survival. Pseudotime and spatial transcriptomic analyses demonstrated that GNAS⁺ epithelial cells occupy terminally differentiated malignant states and specifically localize within spatial niches characterized by hyperactive nucleic acid metabolism and an immunosuppressive TME driven by cancer-associated fibroblasts (CAFs). Mechanistically, GNAS depletion profoundly impaired pyrimidine nucleotide (UMP/UDP) biosynthesis, which sequentially attenuated the activity of the ATF3-JUN-ETS1 transcriptional network, leading to suppressed GC cell proliferation, migration, and invasion, alongside induced apoptosis. Notably, exogenous uridine supplementation successfully rescued these malignant phenotypes, whereas pharmacological inhibition of pyrimidine synthesis (DHODH inhibitor) abolished the oncogenic advantage conferred by GNAS overexpression. GNAS is associated with the malignant evolution of GC by driving pyrimidine metabolic reprogramming and spatially coordinating TME remodeling. Targeting the GNAS-mediated metabolic-transcriptional axis exposes a novel therapeutic vulnerability, offering a promising translational strategy for precision oncology in GC.

Colorectal cancer (CRC) progression from benign polyps to malignant adenocarcinomas is a complex process involving the abnormal proliferation and differentiation of colon epithelial cells. Colorectal adenomas (CRAs), the precursors to most CRCs, are histologically classified into tubular adenomas (TAs), tubulovillous adenomas (TVAs), and villous adenomas (VAs). Despite new findings, the molecular signatures and pathways specific to each adenoma type remain poorly understood. This study aimed to identify specific biomarkers and pathways associated with the progression of TA, TVA, and VA to CRC.

As a non-coding RNA (lncRNA), the RNA component of mitochondrial RNA processing endoribonuclease (RMRP) is implicated in ribosome biogenesis. In recent years, its role in the neurodegenerative system has been reported; however, the molecular mechanism underlying RMRP-mediated neuroprotective effects remains elusive. In the present study, we identified that RMRP expression is regulated by the RNA-binding protein RBM3. The overexpression of RBM3 significantly upregulated RMRP transcription in SH-SY5Y neural cells, whereas RBM3 knockdown led to a marked reduction in RMRP expression. Furthermore, RNA Immunoprecipitation (RIP) assays confirmed the potential interaction between RMRP and RBM3. We then investigated the functional significance of RMRP regulated by RBM3 in Parkinson's disease (PD) cell models. Exogenous overexpression of RMRP strongly attenuated cytotoxicity induced by neurotoxins rotenone (ROT) and MPP+ in SH-SY5Y cells, as evidenced by decreased levels of cleaved poly ADP-ribose polymerase 1 (PARP1) and enhanced cell viability. Given that RBM3 exerts robust neuroprotective effects by accelerating global protein synthesis (GPS), we hypothesized that RMRP is a key mediator of RBM3-conferred neuroprotection. Consistent with this hypothesis, RMRP overexpression enhanced the activity of eukaryotic elongation factor 2 (eEF2), a hallmark of cellular GPS. Its stimulatory effect on GPS was further validated using a puromycin incorporation assay. Collectively, our data reveal that RMRP acts as a novel effector of RBM3 in stimulating cellular GPS and conferring neuroprotective effects in SH-SY5Y cells, providing a new therapeutic target for PD.

Syndecan binding protein (SDCBP) has been shown to be upregulated in esophageal squamous cell carcinoma (ESCC) and predicts poor prognosis in our previous research. SDCBP stimulated the proliferation and tumor formation and may be a target for ESCC. However, the participation of SDCBP in epithelial-mesenchymal transition (EMT) and ESCC metastasis is unclear. In this study, we found that SDCBP promoted the EMT process of ESCC cells and facilitated ESCC metastasis both in vitro and in vivo. Mechanically, SDCBP was found to influence the activation of the Wnt-β-catenin pathway. β-catenin expression and nuclear localization were regulated by SDCBP, accompanied by altered expression of Wnt-β-catenin pathway target genes. Additionally, SDCBP interacted with Y-box binding protein 1 (YBX1) and abnormally upregulated YBX1 in ESCC was responsible for SDCBP-mediated regulation of ESCC migration and invasion. Finally, SDCBP was identified to be transcriptionally regulated by the Wnt-β-catenin pathway. Thus, our study provides a better understanding of the SDCBP-YBX1-Wnt-β-catenin axis in ESCC metastasis and explores a positive feedback loop between SDCBP and the Wnt-β-catenin pathway, offering more compelling evidence for employing SDCBP as a target for ESCC treatment.

Regulatory T cells (Tregs) may influence prognosis in leukemia. This study aimed to explore the effects and mechanisms of Treg subclusters on the prognosis in B-cell acute lymphoblastic leukemia (B-ALL) using single-cell RNA sequencing (scRNA-Seq).

Familial adenomatous polyposis (FAP) is a hereditary condition that almost invariably leads to colorectal cancer. While TP53 inactivation is well established as a late event in the adenoma-to-carcinoma sequence, its functional role during the early stage of colorectal polyp development remains unclear.

One-carbon metabolism has emerged as a critical interface between tumor metabolic adaptation and antitumor immunity. Beyond its canonical role in nucleotide biosynthesis and redox balance, this metabolic network regulates methyl-donor availability, epigenetic programming, and immune-cell state transitions within the tumor microenvironment. Recent studies show that tumor cells can outcompete T cells for methionine, thereby depleting intracellular S-adenosylmethionine, impairing histone methylation, and driving effector dysfunction or exhaustion. At the same time, tumor-intrinsic one-carbon enzymes such as MTHFD2 actively promote immune escape through PD-L1 upregulation and suppression of innate immune sensing. Serine-related pathways further shape the immune landscape in a context-dependent manner, supporting either immunosuppressive cell accumulation or enhanced tumor immunogenicity depending on the cellular compartment and metabolic state. Importantly, one-carbon metabolism also represents a therapeutic opportunity. Strategies including methionine restriction, formate supplementation, serine-pathway targeting, and methyl-donor modulation have shown potential to enhance antitumor immunity and improve responses to immune checkpoint blockade. However, because one-carbon metabolism is required by both tumor cells and immune cells, effective intervention will require careful attention to cell-type specificity, metabolic context, and therapeutic timing. In this review, we discuss how one-carbon metabolism governs T-cell fitness, epigenetic regulation, and the broader tumor immune ecosystem, and we highlight emerging translational strategies for exploiting this pathway in cancer immunotherapy.

Acetyl tributyl citrate (ATBC) is a widely used plasticizer ubiquitously present in the environment. Long-term high-dose ATBC exposure has been associated with reproductive system damage, yet its toxic effects and underlying mechanisms in testicular seminoma remain unclear. This study aimed to investigate the impact of ATBC on the prognosis of testicular seminoma.

Cancer stem-like cells (CSCs) play a pivotal role in driving tumor heterogeneity, therapeutic resistance, and disease progression. Despite the power of single-cell RNA sequencing (scRNA-seq) to resolve intratumoral hierarchies, there remains a need for robust, scalable tools to consistently profile CSCs across both single-cell and bulk transcriptomic data. To address this, we developed ACSCeND-a unified, machine learning-based framework that enables high-resolution CSC state classification and tissue-level deconvolution. ACSCeND comprises (i) a supervised classifier trained on curated scRNA-seq datasets to assign cells into pluripotent-like, multipotent-like, or unipotent-like states, and (ii) an attention-guided autoencoder that deconvolves CSC subtype proportions from bulk RNA sequencing data. Compared to existing tissue deconvolution tools, ACSCeND achieves superior performance, with higher accuracy across synthetic and real-world samples. Applied to over 25 000 tumor profiles from The Cancer Genome Atlas (TCGA), PREdiction of Clinical Outcomes from Genomics (PRECOG), tumor-relapse, and checkpoint inhibitor studies, ACSCeND reveals that CSC abundance strongly correlates with poor disease-free survival and reduced immunotherapy efficacy. Moreover, it uncovers distinct CSC-state-specific molecular programs, offering insights into CSC-driven heterogeneity and tumor evolution. The model also recapitulates known developmental hierarchies in noncancerous tissues, supporting its broader biological relevance. By integrating single-cell precision with bulk-level applicability, ACSCeND offers a robust, interpretable approach to profiling CSC dynamics and establishes CSC state as a clinically meaningful, pan-cancer biomarker for guiding stemness-informed therapies. ACSCeND is available as a python package (through pip) at https://pypi.org/project/ACSCeND/.

A wide spectrum of tumors can affect the gynecologic tract in the context of hereditary cancer syndromes. Over the past two decades, the approach to germline testing initiated by pathologic findings has evolved considerably. This shift began with the identification and integration of specific tumor characteristics and molecular pathways in the most common hereditary syndromes involving the female genital tract, namely, hereditary breast and ovarian cancer syndrome and Lynch syndrome. Subsequently, tumors linked to less common syndromes, such as Peutz-Jeghers syndrome, DICER1 syndrome, tuberous sclerosis complex, hereditary leiomyomatosis and renal cell carcinoma syndrome, and rhabdoid tumor predisposition syndrome type 2 have also been recognized. This review focuses on the clinicopathologic features of these hereditary conditions, with particular emphasis on histologic patterns and genetic testing.

Non-small cell lung cancer (NSCLC) remains a leading cause of global cancer mortality. Increasing evidence implicates aberrant cholesterol metabolic reprogramming as a key facilitator of tumour malignancy; however, the mechanistic connections between lipoprotein metabolism and NSCLC pathogenesis remain elusive. Here, we investigate the unrecognised oncogenic role of cholesteryl ester transfer protein (CETP), a central lipid exchange mediator.

Innate immunity predictors of HIV-1 risk and pathogenesis vary with reproductive hormones, pregnancy, and lactation, yet the underlying mechanisms remain unclear. We hypothesized that pregnancy-associated physiological adaptations alter systemic microRNA (miRNA) expression, thereby regulating immunity, pathogenesis and susceptibility to infection. We analyzed 174 serum samples from 88 participants in a longitudinal cohort from Uganda and Zimbabwe across pre-pregnancy (PP), pregnancy (P), and postpartum breastfeeding (BF). Cell-free peripheral blood miRNAs (n = 2083) were profiled using HTG EdgeSeq. Pregnancy-specific miRNAs were identified by intersecting differentially expressed (DE) miRNAs from P vs. PP and P vs. BF comparisons. miRNA targets and pathways were analyzed using miRWalk, Cytoscape/ClueGO, and cytoHubba. Pregnancy was associated with DE miRNAs (29 upregulated and 131 downregulated) targeting 2733 validated genes. Enriched pathways (FDR < 0.05) included adaptive immune response, Hippo Signaling, Cellular Senescence, HSV-1 infection, and two cancer-related pathways. Pregnancy-enriched targets within each pathway overlapped with the HIV-host interactome by 37-88%. Network analysis identified 47 hub genes interacting with 18 HIV-1 proteins, with Tat and gp120 being most connected viral and HLA-A being the most connected host protein. These findings indicate that pregnancy-driven systemic miRNAs target the HIV-host interactome and specifically identify pregnancy-enriched central hub genes involved in cell cycle control, viral immune evasion and replication to be further investigated for their predictive value in HIV acquisition and pathogenesis in longitudinal cohorts and experimental settings.

Avian viruses formed the foundation of early retrovirology. The historical line extends from the discovery of the first sarcoma virus by Peyton Rous to the quantitative determination of oncogenic activity in cell culture by the focus assay. As a viral group, avian retroviruses offered exclusive advantages that allowed the assembly of a unique and powerful tool chest for the analysis of viral activity. Among the fundamental discoveries facilitated by these tools were viral and cellular oncogenes, cell surface receptors, virus-specific detection of inapparent infection, high-frequency genetic recombination between retroviruses, and the genetic maps of simple retroviruses. The work with avian viruses was soon complemented by research on mammalian retroviruses, and several oncogenes that became the basis of successful targeted therapies were defined. The field of cancer genes is at a point of transition. Future developments will be driven by new technologies and interpretations. They will also require a more comprehensive approach.

Cancer development arises from dynamic interactions between inherited susceptibility and modifiable environmental exposures, among which diet plays a central role. Carotenoids, lipophilic plant-derived pigments including lycopene, α-carotene, and β-carotene, and retinoids, the vitamin A derivatives that regulate gene transcription via retinoic acid receptors (RARs) and retinoid X receptors (RXRs), have been extensively investigated for their chemopreventive and therapeutic potential. This review aims to provide an integrated, mechanism-based synthesis of the roles of lycopene, α- and β-carotene, and retinoids in cancer chemoprevention and to clarify the conditions under which they are most likely to be effective. Beyond summarizing established antioxidant and nuclear-receptor mechanisms, we highlight as a novel emphasis the epigenetic actions of these compounds, including effects on DNA methylation, histone modification, and microRNA regulation, and we integrate these with the well-recognized divergence between dietary and high-dose supplement outcomes. Experimental evidence demonstrates that carotenoids modulate oxidative stress, inflammation, proliferation, apoptosis, angiogenesis, and metastasis through pathways such as Nrf2/ARE, NF-κB, STAT3, Akt/mTOR, MAPK, and Wnt/β-catenin. Lycopene, in particular, exhibits strong antioxidant capacity and multi-target signaling effects, while provitamin A carotenoids additionally influence retinoid-mediated transcriptional programs. Retinoids exert broader differentiation-inducing and antiproliferative effects through direct nuclear receptor signaling and represent one of the few successful differentiation therapies in oncology, most notably in acute promyelocytic leukemia. Epidemiologic studies generally associate higher dietary carotenoid intake with reduced risk of several malignancies, including prostate, breast, lung, colorectal, and gastric cancers. However, randomized trials of isolated high-dose supplementation, particularly β-carotene in smokers, have demonstrated null or harmful effects, highlighting a critical divergence between whole-food dietary patterns and pharmacologic supplementation. In conclusion, carotenoids and retinoids possess biologically plausible anticancer properties, yet their clinical utility remains context dependent. Future research should prioritize biomarker-guided, precision-based strategies, standardized formulations, and whole-food dietary approaches to clarify their role in cancer prevention and treatment.

Breast cancer remains one of the most prevalent malignancies affecting women worldwide and continues to be a leading cause of cancer-related morbidity and mortality. Patients may present with either localized or advanced disease, with clinical outcomes increasingly influenced by molecular subtype and genetic profile. This review highlights the key genetic factors involved in breast cancer, current diagnostic and therapeutic strategies, and promising emerging approaches that may shape future clinical management. Breast cancer diagnosis typically involves clinical breast examination, imaging techniques such as mammography and ultrasound, and confirmatory biopsies. Genetic mutations in specific genes are strongly linked to the development, progression, and metastasis of the disease. Treatment options for localized breast cancer continue to include surgery (lumpectomy or mastectomy) and radiotherapy, combined with systemic therapies tailored to tumor biology, such as endocrine therapy, human epidermal growth factor receptor 2 (HER2)-targeted therapy, and cyclin-dependent kinase (CDK)4/6 inhibitors. For advanced or metastatic breast cancer, recent therapeutic advances include the use of immunotherapy (e.g., immune checkpoint inhibitors), Poly (ADP-ribose) polymerase (PARP) inhibitors for Breast Cancer gene (BRCA)-mutated cancers, antibody-drug conjugates, and novel targeted agents, which have significantly improved patient outcomes in selected populations. Recent findings in breast cancer genetics have highlighted the critical role of germline and somatic mutations, particularly in genes such as BRCA1, BRCA2, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and TP53, in driving tumor initiation, progression, and therapeutic response. Molecular profiling and next-generation sequencing technologies have enabled more precise tumor classification and facilitated the development of personalized treatment strategies. Despite these advances, treatment resistance and disease recurrence remain major challenges, particularly in aggressive subtypes such as triple-negative breast cancer. Consequently, ongoing research is exploring alternative and complementary approaches, including nanotechnology-based drug delivery systems, gene editing techniques such as clustered regularly interspaced short palindromic repeats-Cas9 (CRISPR-associated protein 9) (CRISPR-Cas9), cancer vaccines, and the integration of traditional and plant-derived compounds. These strategies aim to enhance therapeutic efficacy, reduce systemic toxicity, and overcome resistance mechanisms.

As a member of the RNA-binding motif protein (RBM) family, RBM5 is a characterized tumor suppressor in lung and prostate cancers, with critical roles in alternative splicing of apoptosis- and cell cycle-related genes. However, its direct capacity to regulate gene transcription remains unreported. Here, we identified that RBM5 was significantly downregulated in breast cancer cells and clinical specimens, especially in the basal-like subtype. RBM5 overexpression attenuated breast cancer cell malignancy, while RBM5 knockdown exerted opposite effects. Among genes with promoter G-quadruplex (G4) motifs, RBM5 was positively correlated with multiple tumor suppressors, including BAP1, but uncorrelated with the oncogene MYC. RBM5 bound to G4 motifs in both MYC and BAP1 promoters, but differentially modulated G4 structure stability: it destabilized MYC-G4 while stabilizing BAP1-G4. Mechanistically, either the RRM1 or the RRM2 domain was sufficient for MYC-G4 binding, whereas both domains were required for BAP1-G4 interaction. RBM5 manipulation regulated endogenous BAP1 but not MYC expression. BAP1 overexpression reversed the protumorigenic effects of RBM5 knockdown in cellulo and tumor growth in a xenograft mouse model. Collectively, we reveal that RBM5 acts as a breast cancer tumor suppressor via directly binding the BAP1 promoter G4 to transcriptionally activate BAP1 expression.