One of the most prevalent oral cancers, oral squamous cell carcinoma (OSCC), is distinguished by its rapid growth, invasiveness, and high metastatic potential. Green AgNPs are important because they can reduce systemic toxicity by inducing oxidative stress, cytotoxicity, and apoptosis in cancer cells. The goal of this study was to use saponins as natural stabilizers to create AgNPs, and the detrimental apoptotic effects on cancer cells were examined using high-content screening (HCS) assays such as TNI, CMP, and VCC.

HPV types 16 and 18 are associated with 70% of invasive cervical cancers. Between these two types of HPV, HPV type 16 is more commonly found in cervical cancer patients, whereas HPV type 18 is less frequently reported. Currently, the molecular mechanism underlying the increased cancer risk in HPV type 16, compared to HPV type 18, has not yet been fully elucidated.

Acute lymphoblastic leukemia (ALL) is one of the most common malignancies worldwide. The long non-coding RNA MEG3 functions as a tumor suppressor in several cancers, potentially influencing gene expression through transcriptional, translational, and epigenetic mechanisms. let-7i plays a role in leukemia progression. This study aimed to evaluate MEG3 gene expression in adult ALL patients and investigate its possible regulatory interaction with let-7i-3p and let-7i-5p.

This study aimed to create a genetic and clinical roadmap for the TGF-β pathway in an Iraqi population, focusing on the TGF-β1 (+869 C/T) polymorphism.

Lymphoma is the most common hematologic malignancy in Thailand, with diffuse large B-cell lymphoma (DLBCL) being the predominant subtype. Early prognostic indicators are essential for guiding clinical decisions. Genetic alterations, particularly in regulatory regions, may serve as potential biomarkers. This study investigated sequence alterations upstream of exon 1 of the OSBPL10 gene and their clinical relevance in a Northern Thai DLBCL population.

A key element of computational drug discovery is the precise prediction of drug-gene interactions, particularly when working with intricate biological systems where relational dependencies are essential. Because biological networks are graph-structured, traditional machine learning techniques frequently fall short. Graph Neural Networks (GNNs) have emerged as a viable approach for learning meaningful representations from this data type in response to this challenge. In this study, three state-of-the-art GNN architectures Graph Convolutional Networks (GCN), Graph Attention Networks (GAT), and GraphSAGE are comprehensively compared using a bipartite graph constructed from drug-target biochemical activity data.

The present study was planned to examine the possible association of polymorphisms in the superoxide dismutase and catalase genes with adverse normal tissue effects or injury resulting from radiotherapy in HNC patients.

The aim of the study was to determine how the chemotherapeutic alkylating agent dacarbazine, together with the application of the miR-204-5p mimic in vivo, affects the presence of disseminated melanoma cells in distant organs - the lungs and liver.

Life-prolonging targeted therapies are available based on alterations detected on next-generation sequencing (NGS); however, clinical data on NGS adoption are limited.

IntroductionCurrent cervical cancer screening guidelines recommend colposcopy referral for women co-positive for high-risk human papillomavirus (hrHPV) and abnormal cytology (≥ASC-US). However, cytology exhibits suboptimal sensitivity, and this strategy leads to high colposcopy burdens, especially in populations where non-HPV16/18 genotypes predominate. We evaluated a novel triage strategy using HPV16/18 genotyping and PAX1 methylation to optimize resource allocation.MethodsThis was a retrospective cohort study. In a cohort of 3,233 hrHPV-positive women who underwent HPV genotyping, liquid-based cytology (TCT), PAX1 methylation testing, colposcopy, and histopathological confirmation, we compared two strategies: (A) standard referral (hrHPV+ & TCT ≥ ASC-US); (B) novel referral (HPV16/18+ → immediate colposcopy; non-16/18 hrHPV+ → colposcopy if PAX1 methylation ΔCt ≤ 8.79). CIN3+ (CIN3 or cancer) served as the clinical endpoint.ResultsNon-16/18 hrHPV types (especially HPV52/58) accounted for over 30% of infections and 60% of CIN2+ lesions. PAX1 methylation was strongly associated with lesion severity (median ΔCt: chronic cervicitis 17.92 vs. CIN3 7.36 vs. cancer 5.97; P < 0.001) and predicted CIN3+ with high accuracy (AUC = 0.82 in non-16/18 group). Strategy B detected 40 additional CIN3+ cases (+30.5%), reduced colposcopy referrals by 853 cases (absolute -25%, relative -46%), and increased the positive predictive value (PPV) from 6.6% to 14.6% (2.2-fold improvement) compared to Strategy A.ConclusionA triage algorithm combining HPV16/18 genotyping with PAX1 methylation significantly enhances CIN3+ detection while substantially reducing immediate colposcopies. This strategy is particularly well-suited for Chinese and other Asian populations where non-16/18 hrHPV types are prevalent, offering a more precise, cost-effective approach toward WHO's 2030 cervical cancer elimination goals.

Although cisplatin (CDDP) is widely employed in combination immunotherapy, no CDDP-based regimen has shown a survival benefit when treating the ovarian cancers. This is mainly because the impact of CDDP on immunotherapy is not fully understood. A critical gap concerns how CDDP reshape the tumour microenvironment, especially through extracellular vesicles (EVs)-mediated communication. In this work, using human and murine ovarian cancer cells as a model, we demonstrate that CDDP boosts the secretion of EVs from cancer cells, while exerting no such effect on non-cancerous cells. These CDDP-induced tumour-derived EVs, in turn, drive the differentiation of CD4+ T cells towards immunosuppressive regulatory T cells (Treg cells), which are known to limit the efficacy of immunotherapy. Based on next-generation sequencing, a significant enrichment of miR-181a-5p was identified in CDDP-induced tumour-derived EVs, and further functional studies confirmed that this microRNA promoted Treg cell differentiation via suppressing sirtuin 1 (SIRT1), a key regulator of the transcription factor forkhead box protein P3 (FOXP3). Importantly, inhibition of miR-181a-5p abrogated the Treg-promoting effect of CDDP-induced tumour-derived EVs, a finding further validated in vivo, where blockade of miR-181a-5p not only impaired Treg differentiation but also restored T-cell-mediated antitumour immunity and restrained tumour growth. Together, these findings uncover a previously unrecognised mechanism by which CDDP exacerbates immunosuppression via miR-181a-5p-enriched EVs and suggest that targeting this pathway could improve the therapeutic efficacy of combination immunotherapy in ovarian cancer.

Hepatocellular carcinoma (HCC) remains a major global health burden with limited therapeutic options and poor prognosis. PDRG1 is upregulated in several malignancies, yet its clinical relevance and mechanistic role in HCC are not fully understood. Here, we investigated the contribution of PDRG1 to HCC progression and delineated the underlying molecular mechanism. Using public datasets, patient specimens, in vitro functional assays, and subcutaneous xenograft models, we evaluated PDRG1 expression, biological functions, and downstream pathways. Transcriptome profiling, pathway enrichment analysis, rescue experiments, co-immunoprecipitation, and ChIP-qPCR were performed to define the PDRG1-EZH2-p21 axis. PDRG1 was significantly upregulated in HCC tumor tissues compared with adjacent non-tumor liver tissues and was associated with worse patient survival. Functionally, PDRG1 enhanced HCC cell proliferation, migration, invasion, colony formation, and tumor growth in vivo. RNA-seq and enrichment analyses identified cellular senescence as a prominent downstream program regulated by PDRG1. Mechanistically, PDRG1 directly interacted with EZH2, increased H3K27me3 enrichment at the p21 promoter, and suppressed p21 transcription. Restoration of p21 expression attenuated the oncogenic effects of PDRG1, whereas EZH2 overexpression rescued the impaired malignant phenotypes caused by PDRG1 knockdown. Domain-mapping further indicated that the N-terminal residues 36-70 of PDRG1 contribute to its interaction with EZH2. Collectively, our findings identify PDRG1 as a clinically relevant oncogene in HCC and reveal an epigenetic mechanism by which PDRG1 cooperates with EZH2 to repress p21 and bypass senescence. The PDRG1-EZH2-p21 axis may represent a potential biomarker and therapeutic target for HCC.

Triple-negative breast cancer (TNBC), a distinct breast cancer subtype, poses significant challenges to conventional therapeutic approaches, and effective targeted therapies are limited. CRISPR/Cas9 library screening has demonstrated unprecedented efficiency and revolutionary potential in the identification of therapeutic targets. In this study, we performed In vivo CRISPR/Cas9 library screening and identified the E2 ubiquitin-conjugating enzyme UBE2L3 as a critical regulatory factor in the progression of TNBC. Loss of UBE2L3 restricted tumor cell growth by modulating autophagy in TNBC cells. Mechanistically, UBE2L3 downregulation led to increased tuberous sclerosis complex 2 (TSC2) expression, suppressing mTOR activity and altering autophagic processes in tumor cells. This regulation was mediated through the interaction between UBE2L3 and the E3 ubiquitin ligase SMURF2, which together control TSC2 protein ubiquitination and degradation. Autophagy and the tumor microenvironment are closely associated, and we observed that UBE2L3 knockdown in TNBC tumors significantly increased CD8+ T lymphocyte infiltration and enhanced tumor sensitivity to anti-PD-1 therapy. Collectively, our findings provide a theoretical foundation for considering UBE2L3 as a potential therapeutic target in TNBC.

Colorectal cancer (CRC) is among the most common cancers worldwide. Cellular senescence, characterized by an irreversible state of growth arrest, has been recognized as a promising therapeutic strategy for combating cancer. Here, the oncogenic role of Chromobox homolog 8 (CBX8) in CRC and its regulatory mechanisms in cell senescence and transcriptional regulation were systematically investigated. We demonstrated that CBX8 deficiency suppresses colorectal tumorigenesis and promotes tumor cell senescence in both in vivo and in vitro models. Mechanistically, CBX8 inhibits autophagy-dependent senescence in CRC by modulating the mTOR signaling pathway through transcriptional repression of DDIT4, a known negative regulator of mTOR. CBX8 achieves this by recruiting TRIM28 to bind the promoter region of DDIT4, thereby maintaining the H3K27me3 modification status and repressing expression of DDIT4. Furthermore, our findings highlight the therapeutic potential of CBX8 inhibitors in combination with senescence-targeting agents, which significantly enhances antitumor effects in CRC xenograft models. These results provide novel insights into the molecular mechanisms underlying CRC progression and underscore the potential of CBX8 as a therapeutic target for developing targeted therapies and senolytic-based anticancer strategies. This study advances our understanding of CRC pathogenesis and offers promising directions for precision medicine in CRC treatment.

Renal cell carcinoma (RCC) is a metabolic disorder and VHL gene inactivation is recognized as a crucial event in RCC progression. Investigating the specific metabolite that differ in VHL-mutant RCC and understanding how VHL regulates the metabolite may offer new insights into the underlying mechanisms of RCC. First, we employed untargeted metabolomics and ELISA to identify and confirm the differential metabolite in the plasma and tumor tissues of VHL-mutant RCC patients. Then, we demonstrated the importance of the differential metabolite in RCC progression through cell phenotype and animal experiments. Finally, we utilized western blotting, immunoprecipitation, ubiquitination modification proteomics, TMT proteomics, and RNA sequencing to elucidate the regulatory mechanisms of VHL on the metabolite. By analyzing the metabolomics data from plasma and tumor tissues alongside subsequent expression validation, we identified L-Asparagine (L-Asn) as the differential metabolite in VHL-mutant RCC, with its levels significantly decreased in these tumors. L-Asn was found to promote the growth and metastasis of RCC cell lines and mouse orthotopic renal tumors. Mechanistically, VHL interacted with L-Asparagine synthase (ASNS) and facilitated its ubiquitination, leading to decreased ASNS expression, and ASNS overexpression activated PI3K-AKT and MAPK signaling pathways by binding to Junction plakoglobin (JUP) and inhibiting its expression. Conversely, use of an ASNS inhibitor significantly restrained the growth and metastasis of RCC cells in vitro and in vivo. In summary, our findings highlighted the critical role of L-Asn in RCC and identified ASNS as a novel substrate for VHL-mediated ubiquitination, presenting a potential new target for RCC treatment.

The development of novel therapeutic strategies for advanced and metastatic hepatocellular carcinoma (HCC) remains an urgent clinical need. Despite suboptimal efficacy, the breakthrough of tyrosine kinase inhibitors in HCC treatment therapy underscores the advantage of targeted therapy. Therefore, innovative targeted therapies are urgently needed to enhance treatment efficacy, decrease recurrence rates, and improve patient survival outcomes. The forkhead box M1 (FOXM1) transcription factor serves as a master regulator of oncogenic signaling networks that drive cancer progression. Our study identified budding uninhibited by benzimidazoles 1 (BUB1) as a crucial downstream effector of FOXM1, with demonstrated direct protein-protein interaction. Moreover, FOXM1 directly bound to the GTAAACC motif at the -293 bp region of the BUB1 promoter and activated its transcription, thereby driving HCC cell proliferation. Mechanism studies have shown that the FOXM1/BUB1 axis regulated multiple oncogenic processes in HCC, including cell proliferation, DNA repair, G2/M cell cycle transition, stemness, invasion, and migration. Knockdown of BUB1 significantly sensitized HCC cells and xenograft tumors to the FOXM1 inhibitor FDI-6. Furthermore, combined pharmacological inhibition of FOXM1 (FDI-6, RCM-1, thiostrepton) and BUB1 (BAY-1816032) synergistically inhibited the proliferation of HCC cells and xenograft tumors. These findings establish FOXM1-mediated BUB1 upregulation as a key driver of HCC malignancy. Targeting the FOXM1/BUB1 axis represents a promising therapeutic strategy for the treatment of advanced and metastatic HCC, offering new opportunities for HCC therapy.

High mobility group AT-hook 1 (HMGA1) is a chromatin regulator overexpressed in various cancers, often predicting poor outcomes. However, its role in head and neck squamous cell carcinoma (HNSCC) remains unclear. A hallmark of HNSCC is the rapid growth of its vasculature. Here, we identify an epigenetic mechanism whereby HMGA1 promotes tumor progression and angiogenesis via upregulation of fibroblast growth factor-binding protein 1 (FGFBP1). HMGA1 silencing suppressed oncogenic properties in vitro and reduced tumor initiating cells in HNSCC xenograft mice. RNA sequencing revealed that HMGA1 regulated transcriptional networks involved in tumor progression and angiogenesis, including the FGFBP1 gene. HMGA1 directly binds to the FGFBP1 promoter to induce its expression. This upregulation increased secretion of FGFBP1's target, FGF2. Interestingly, disrupting FGFBP1 via gene silencing or the FGFR1 inhibitor PD166866 recapitulated phenotypes observed with HMGA1 silencing. Blocking HMGA1, FGFBP1, or FGFR1 also reduced stromal formation and increased tumor necrosis. In human HNSCC, the combined analysis of HMGA1 and FGFBP1 provides a more detailed evaluation of patient prognosis. Our findings highlight a novel paradigm where HMGA1 and FGFBP1 drive tumor progression and angiogenesis, presenting them as potential therapeutic targets for HNSCC.

Immune checkpoint pathways are central to tumor immune evasion, and genetic variants of programmed death-1 (PD-1) may influence cancer susceptibility. This study evaluates the association between the PD-1.5 (rs2227981) polymorphism and the risk of bladder cancer (BC) in the Turkish population.

Urological malignancies, primarily including renal cell carcinoma, bladder cancer and prostate cancer, underscore the critical importance of early screening, diagnosis and treatment in inhibiting disease progression and improving patient prognosis. Advancements in molecular biology have established urinary biomarkers as promising noninvasive tools with considerable potential for early tumour detection and screening high-risk populations, potentially overcoming limitations associated with traditional invasive procedures and imaging. This review systematically summarises urinary biomarkers related to renal cell carcinoma, bladder cancer and prostate cancer. It focuses on protein biomarkers (e.g., cytokeratin and nuclear matrix protein 22), epigenetic and transcriptional biomarkers (e.g., microRNAs and long noncoding RNAs), genetic biomarkers (e.g., telomerase reverse transcriptase and fibroblast growth factor receptor 3) and emerging biomarkers (metabolomic markers, circulating tumour DNA and mass spectrometry-based high-throughput proteomics). This review provides an in-depth exploration of the molecular mechanisms, diagnostic performance (sensitivity and specificity), current clinical applications and limitations of various biomarkers, placing a particular emphasis on comparing the differential expression of the same biomarker across different cancer types. By building on this foundation, this review further outlines future development pathways, including multibiomarker combination strategies, AI-assisted analysis and standardised testing protocols, to offer comprehensive references for the early, noninvasive and precise diagnosis of urological tumours.

Urological cancers, such as prostate, bladder and renal cell carcinoma, contribute substantially to the global cancer burden. Their management remains challenging due to extensive molecular and clinical heterogeneity. Conventional single-omics approaches (e.g., genomics and transcriptomics) have led to important discoveries but provided only partial views of tumour biology, which limit the robustness of biomarkers and therapeutic precision. Multi-omics integration offers a systems-level perspective that captures the complex regulatory networks underlying tumour initiation, progression and treatment resistance.