The cervicovaginal microbiome (CVMB) is pivotal in maintaining the homeostasis of the lower female genital tract and has emerged as a significant modulator of cervical carcinogenesis. Although persistent infection with high-risk human papillomavirus (HR-HPV) is a prerequisite for the development of cervical intraepithelial neoplasia (CIN) and subsequent cervical carcinoma, it remains insufficient alone to drive oncogenesis. Accumulating evidence suggests that alterations in the CVMB composition profoundly impact HPV persistence, local immune responses, and disease progression. A vaginal microbiota dominated by Lactobacillus species, most notably Lactobacillus crispatus, correlates with low microbial diversity, robust immune regulation, and facilitated HPV clearance. Conversely, microbial dysbiosis-characterized by Lactobacillus depletion and a concomitant proliferation of anaerobic taxa, typical of Community State Type (CST) IV and Lactobacillus iners-dominated profiles-is strongly associated with chronic inflammation, oxidative stress, epithelial barrier compromise, and an elevated risk of CIN progression. This review synthesizes current evidence regarding the multifaceted interactions among the cervicovaginal microbiome, HPV pathogenesis, immune dysregulation, and oxidative stress in the etiology of CIN. Elucidating these intricate host-microbiome dynamics may precipitate the discovery of novel microbiome-derived biomarkers, ultimately informing innovative prophylactic and therapeutic interventions for cervical cancer.

WD repeat and HMG-box DNA-binding protein 1 (WDHD1) has been identified as a crucial oncogene in various tumors, but its role in pancreatic cancer remains unexplored. This study investigated the mechanisms by which WDHD1 contributes to pancreatic cancer progression. Differential analysis of the Cancer Genome Atlas (TCGA) pancreatic cancer samples identified abnormally expressed genes. Cellular assays, including cell proliferation, flow cytometry, and apoptosis assays, demonstrated WDHD1's oncogenic role. WDHD1 expression was significantly elevated in pancreatic cancer cells and tissues compared to normal counterparts. Knockdown of WDHD1 inhibited cell proliferation, induced apoptosis, and caused G1-phase cell-cycle arrest. In vivo xenograft models further validated that WDHD1 knockdown suppressed the growth of pancreatic cancer cells. Mechanistically, WDHD1 knockdown resulted in significant reductions in CDK4 and cyclin D1 protein levels, whereas WDHD1 overexpression produced the opposite effects. Additionally, E2F1 overexpression increased the expression of WDHD1 at both mRNA and protein levels. Rescue experiments revealed that WDHD1 knockdown could reverse the E2F1-induced upregulation of CDK4 and cyclin D1 protein levels. In conclusion, E2F1 promotes pancreatic cancer cell proliferation and cell-cycle progression by upregulating WDHD1, which in turn enhances the expression of the CDK4-cyclin D1 complex.

Multicellular cancer cell aggregates, termed spheroids, are anoikis-resistant, avascular, heterogeneous structures responsible for transcoelomic metastasis of ovarian clear cell carcinoma (OCCC). OCCC is a rare subtype of ovarian cancer with high ARID1A gene mutation rates, resulting in genome-wide changes to H3K27Ac levels and histone deacetylase (HDAC) function. Our study investigated the utility of HDAC inhibitor (HDACi) treatment and H3K27Ac dynamics in OCCC spheroids. By comparing KOC-7c and 105C OCCC cell lines, which have opposing abilities to proliferate as spheroids, we revealed that KOC-7c and 105C spheroids differentially regulated H3K27Ac levels, which correlated with the sensitivity of KOC-7c and the resistance of 105C spheroids to H3K27Ac-altering HDACi treatment. RNA-seq of Entinostat-treated versus vehicle-treated spheroids resulted in a dramatic change in the 105C spheroid transcriptome such that it more closely resembled the proliferative KOC-7c transcriptome over the short term. Comparative pathway analysis identified preferential de-repression of a G2/M checkpoint gene program in 105C spheroids upon Entinostat treatment when compared directly to the KOC-7c spheroids. Our results suggest that the utility of HDACi in OCCC is highly context-dependent.

Despite substantial advances in our understanding of cancer metastasis, it remains the leading cause of mortality among cancer patients. Elucidating the molecular mechanisms that drive metastatic progression is expected to facilitate the development of more effective therapeutic strategies. Among the numerous candidates, the long non-coding RNA H19 and its derivative miR-675 have been increasingly recognized as key regulators of metastatic dissemination in cancers of diverse tissue origins. In this review, we provide an up-to-date overview of the H19/miR-675 axis in metastatic progression, with particular emphasis on its involvement in the dynamic and complementary processes of epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET). We also highlight the opportunity to consider the H19/miR-675 axis as promising biomarkers and potential therapeutic targets.

Hepatocellular carcinoma (HCC) shows high incidence and mortality worldwide. TRIM26, an E3 ubiquitin ligase within the TRIM family, exerts regulatory functions in various tumors. This study analyzed the expression patterns and potential functions of TRIM26 in HCC based on transcriptomic data.

First, the differential expression of TRIM26 between tumor and normal tissues was analyzed using the TCGA dataset and cross-validated using TIMER 2.0 and HCCDB. Enrichment analysis evaluated its association with hallmark pathways including Wnt/β-catenin. A gene functional interaction network was built via GeneMANIA to explore TRIM26 and the Wnt/β-catenin pathway. Immune cell infiltration was quantified by ssGSEA for immune microenvironment correlation. scRNA-seq data established an HCC single-cell atlas to define TRIM26 distribution across cell subsets. AUCell was used to assess TRIM26-pathway associations within specific cell types.

TRIM26 was significantly upregulated in HCC tissues, and its high expression correlated with enrichment of oncogenic pathways including Wnt/β-catenin, G2/M checkpoint, and TGF-β. GeneMANIA showed that TRIM26 interacted directly or indirectly with Wnt/β-catenin core molecules, implying its regulatory role. TRIM26 expression was closely linked to infiltration of activated B cells, CD8⁺ T cells, and NKT cells. Single-cell analysis revealed TRIM26 was mainly expressed in hepatocytes, T/NK cells, myeloid cells, and B cells. Importantly, in hepatocytes, TRIM26 strongly correlated with Wnt/β-catenin activity, which was much higher in tumor hepatocytes than normal ones.

In HCC, TRIM26 was abnormally overexpressed. TRIM26 may regulate tumor progression via the Wnt/β-catenin pathway and is linked to immune infiltration. Thus, TRIM26 is a potential therapeutic target for HCC.

Triple-negative breast cancer (TNBC) is characterized by aggressive progression and poor prognosis, partly due to abnormal angiogenesis. While the metabolic reprogramming of tumor cells is well characterized, the metabolic regulation of tumor-associated endothelial cells (ECs) remains unclear. Here, we identified the mitochondrial deacylase SIRT5, which has established tumor-promoting roles in TNBC cells, as a key regulator of endothelial metabolic homeostasis and tumor angiogenesis. SIRT5-deficient host mice showed significant defects in supporting the growth of orthotopic SIRT5-proficient mammary tumor transplants, and the resulting neoplasms showed defects in tumor vascularization. In a 3D microfluidic vessel-on-chip model, SIRT5 loss compromised vascular barrier integrity and EC sprouting. Mechanistically, SIRT5 -deficient ECs exhibited diminished mitochondrial respiratory capacity but apparently normal glycolysis. SIRT5 loss also caused increased mitochondrial reactive oxygen species levels, and a mitochondrial antioxidant rescued the endothelial cell defects following SIRT5 loss, indicating that SIRT5-mediated mitochondrial redox homeostasis in the tumor microenvironment is necessary to maintain vascular function. Orthotopic co-transplantation of TNBC and EC cells with or without SIRT5 knockdown demonstrated that endothelial SIRT5 promotes increased tumor growth in vivo . These results suggest that targeting SIRT5 offers a potential therapeutic strategy to disrupt tumor angiogenesis and suppress TNBC progression by targeting the metabolic vulnerabilities of the tumor endothelium.

Exposure to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) may promote the initiation and progression of prostate cancer (PCa); however, its precise molecular mechanisms remain unclear.

By integrating network toxicology, bioinformatics, and machine learning algorithms, potential molecular targets of PhIP in PCa were identified. Their biological significance was comprehensively evaluated through immune infiltration analysis, single-cell analysis, high-precision molecular docking, molecular dynamics simulations, and experimental validation.

A total of 17 candidate genes associated with PhIP-induced PCa were identified. SHAP analysis identified SLC14A1 as the dominant contributor to model performance. Molecular docking and molecular dynamics simulations suggested that PhIP could form a stable, high-affinity complex with SLC14A1. Experimental validation showed that PhIP exposure induced cytotoxicity and was associated with decreased SLC14A1 expression, while immune infiltration and single-cell analyses further indicated its close association with the tumor immune microenvironment and epithelial localization.

This study offers valuable insights into the potential risks of PhIP exposure in PCa. The key genes and pathways identified may serve as potential biomarkers and therapeutic targets, providing new directions for future research and public health strategies.

Regulatory B cells (Bregs) are critical in regulating immune responses and fostering immune tolerance in various cancers; however, their role in head and neck squamous cell carcinoma (HNSCC) is unclear. This study examined the function of Breg-related genes in HNSCC and their possible prognostic and therapeutic implications.

The Cancer Genome Atlas (TCGA)-HNSCC training cohort was used to establish a prognostic signature for Breg-related genes by applying consensus clustering, univariate Cox regression, least absolute shrinkage and selection operator (LASSO) Cox regression, and multivariate Cox regression analyses. Validation cohorts from the TCGA and Gene Expression Omnibus (GEO) databases were used to assess the robustness of the model. This study investigated the associations among the signature and several clinicopathological features, expression of immune checkpoints, tumor mutation burden (TMB), and sensitivity to pharmacological agents. The underlying mechanisms were examined using weighted gene co-expression network analysis (WGCNA) and gene set enrichment analysis (GSEA). Additionally, various techniques, including ESTIMATE, were used to assess immune infiltration. Functional experiments and transcriptome sequencing were conducted to investigate the role of oxidized low-density lipoprotein receptor 1 (OLR1) gene.

The analysis identified an eight-gene Breg-related prognostic signature that demonstrated robust predictive power across cohorts. High-risk patients exhibited significantly poorer survival, reduced immune cell infiltration, and lower immune molecule expression. The prognostic accuracy was further improved by integrating the risk score with TMB or clinicopathological features. Functional analyses revealed strong associations with immune-related pathways. Moreover, the signature was reported as a potential biomarker for predicting immunotherapy response and drug sensitivity. Furthermore, OLR1, the most essential gene of the signature, was found to be oncogenic and linked to immune evasion in HNSCC.

The Breg-related gene signature provides an effective prognostic tool for patients with HNSCC, reflects the immune landscape and TMB, and may direct personalized therapeutic approaches, such as immunotherapy.

The tumor microenvironment in solid tumors is characterized by extracellular acidosis, which promotes cancer aggressiveness. In osteosarcoma, the most common primary bone cancer, a highly acidic tumor microenvironment is associated with metastasis and poor prognosis, partly due to metabolic rewiring, including changes in lipid pathways such as those involving sphingosine-1-phosphate, a bioactive sphingolipid. Sphingosine-1-phosphate has been previously implicated in histone deacetylase inhibition and gene activation. Here, we investigated whether acidosis induces nuclear sphingosine-1-phosphate accumulation via sphingosine kinase 2, leading to epigenetic activation of oncogenes like FOS in osteosarcoma.

Osteosarcoma spheroids were cultured under neutral or acidic conditions. Histone H3 acetylation was assessed by capillary Western blotting. FOS expression and FOS nuclear localization were analyzed. Sphingosine-1-phosphate's role was addressed through sphingosine kinase 2 silencing and inhibition (ABC294640). Functional effects were measured using colony formation assays. Patient-derived OS tissues (n = 7) were analyzed for correlations between acidity markers (LAMP2, V-ATPase), sphingosine kinase 2, and FOS expression.

Acidosis increased both sphingosine kinase 2 mRNA expression after 24 h and histone H3 acetylation, which followed progressive FOS upregulation and nuclear FOS accumulation. Sphingosine kinase 2 inhibition or silencing reduced these effects and impaired clonogenicity. In patient tissues, sphingosine kinase 2 levels correlated with acidosis markers and FOS expression.

We identified a novel mechanism where acidosis stimulates both nuclear sphingosine kinase 2 to synthesize sphingosine-1-phosphate and histone H3 acetylation, ultimately leading to FOS transcription. Targeting this axis decreased clonogenesis, underscoring its therapeutic potential in osteosarcoma and potentially other acid-adapted cancers.

To evaluate the effect sizes of factors influencing quality of life among colorectal cancer survivors.

This study was a systematic review and meta-analysis.

This study was conducted according to PRISMA guidelines. Ten international and Korean databases, including Web of Science, PubMed, SCOPUS, were searched from January 2000 to October 2024. Methodological quality was assessed using the JBI Critical Appraisal Checklist. Effect sizes (Esr) were calculated using Fisher's Z transformation. Publication bias was evaluated using Egger's test, funnel plots, and trim-and-fill methods.

Physical factors included fatigue (ESr -0.567) and symptom experiences (ESr -0.474). Psychological distress showed the strongest negative association (ESr -0.737), followed by depression (ESr -0.590). Self-efficacy (ESr 0.640), resilience (ESr 0.439), and body image (ESr 0.412) demonstrated positive associations. Social support was positively associated (ESr 0.381).

Quality of life among colorectal cancer survivors is associated with physical, psychological, and social factors including fatigue, symptoms, distress, depression, self-efficacy, resilience, body image, and social support.

No patient or public involvement in this systematic review and meta-analysis.