BUB3 is a core component of the spindle assembly checkpoint (SAC) that is indispensable for faithful chromosome segregation and mitotic progression. Although aberrant BUB3 expression has been reported in several malignancies, its comprehensive role in tumorigenesis, immune regulation, and therapeutic response across cancers remains poorly understood. This study aimed to systematically characterize the expression landscape, clinical significance, biological functions, and therapeutic relevance of BUB3 in a pan-cancer context. A comprehensive pan-cancer analysis integrating multiple public databases and bioinformatics platforms was performed to evaluate the expression pattern, diagnostic performance, prognostic value, genomic alterations, functional pathways immune infiltration characteristics, and drug sensitivity associated with BUB3. In addition, BUB3 expression in hepatocellular carcinoma (LIHC) was validated using RT-qPCR and Western blotting, and its biological functions were further investigated through in vitro experiments. BUB3 was significantly upregulated in most cancer types and exhibited strong diagnostic performance in several malignancies. Elevated BUB3 expression was associated with unfavorable clinical outcomes, especially in head and neck squamous cell carcinoma (HNSC), LIHC, and lung adenocarcinoma (LUAD). Genetic alterations in BUB3, predominantly mutations, were frequently observed in uterine corpus endometrial carcinoma (UCEC). Copy number variation (CNV) and tumor mutation burden (TMB) positively correlated with BUB3 expression in LUAD. Functional enrichment analyses suggested that BUB3-related genes are primarily involved in cell cycle regulation, proliferation, migration, and invasion pathways. Moreover, BUB3 expression was closely associated with immune cell infiltration patterns, while single-cell analyses demonstrated predominant BUB3 expression in immune populations, particularly T cells, indicating a potential role in remodeling the TIME. Importantly, elevated BUB3 expression was associated with reduced responsiveness to immunotherapy and decreased chemosensitivity, suggesting unfavorable therapeutic outcomes in patients with high BUB3 expression. Experimental validation further demonstrated increased BUB3 expression in LIHC tissues and cell lines. Functional assays revealed that BUB3 knockdown significantly inhibited colony formation, proliferation, migration, and invasion in HepG2 and Hep3B cells, supporting its oncogenic role in LIHC progression. Our findings demonstrate that BUB3 plays a critical role in tumor progression and immune regulation and possesses substantial diagnostic and prognostic value, highlighting its potential as both a biomarker for patient stratification and a promising therapeutic target across multiple cancer types.
Xiaona Liu, Yajie Qi, Xinyi Dang et al.· European Journal of Medical...· 0 citations
BACKGROUND
The DExD/H-box (DDX) helicase family plays critical roles in RNA metabolism and has been implicated in tumorigenesis. However, the pan-cancer activities and prognostic potential of DDX52, especially in liver hepatocellular carcinoma (LIHC), are largely unknown.
METHODS
We comprehensively analyzed DDX52 across pan-cancer using TCGA, GEO, HPA, and SpatialTME databases, assessing its differential expression, prognosis, genetic alterations, Tumor Mutational Burden (TMB), Microsatellite Instability (MSI), and immune microenvironment features. In LIHC, we performed functional enrichment, PPI network, single-cell sequencing, and drug sensitivity analyses. Molecular docking explore potential small-molecule inhibitors of DDX52. Finally, we validated DDX52 expression and function in LIHC.
RESULTS
DDX52 mRNA and protein expression were significantly upregulated in multiple malignancies, including LIHC. Elevated DDX52 expression correlated with poor prognosis in LIHC. Genetic analysis revealed frequent copy number variations (CNV) and single-nucleotide variants (SNV) of DDX52, with significant positive correlations between DDX52 expression and both TMB and MSI across numerous cancer types. DDX52 expression was also significantly associated with immune cell infiltration, immune checkpoint molecules. In LIHC, DDX52 was predominantly expressed in B cells, proliferating T cells, malignant cells, and monocytes/macrophages. Functional enrichment analysis indicated DDX52 involvement in metabolic processes, histone modification, cell cycle regulation, and oncogenic signaling pathways. Pharmacologically, high DDX52 expression correlated with reduced drug sensitivity. Experimentally, DDX52 silencing significantly inhibited proliferation, colony formation, migration, and invasion in HepG2 and MHCC-97H cells.
CONCLUSIONS
Our integrative analyses and experimental validation suggest that DDX52 is a potential prognostic biomarker and therapeutic target in LIHC. Its associations with immune features and multiple cancer-related pathways provide hypotheses for future mechanistic investigation.
Chongyu Zhang, Qiankun Wang, Mengchen Zhu et al.· Molecular and Cellular Probe...· 0 citations
Background Chromosome 17 Open Reading Frame 75 (C17orf75) encodes the protein Njmu-R1 (Protein Njmu-R1),, which is involved in intracellular vesicle trafficking; however, its role in tumor progression remains largely unclear. Methods Public datasets from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and the Human Protein Atlas (HPA) were analyzed to evaluate the expression profile, mutation landscape, and diagnostic and prognostic value of C17orf75. Bioinformatics analyses were subsequently performed to explore its associations with immune infiltration. In addition, functional assays were conducted on Hep3B and MHCC-97H cells, and immunohistochemistry (IHC) was performed on clinical liver hepatocellular carcinoma (LIHC) samples. Results C17orf75 was significantly upregulated in multiple cancer types, particularly in LIHC. Elevated C17orf75 expression was associated with unfavorable prognosis and advanced clinicopathological features in LIHC. Functional enrichment analyses indicated that C17orf75-related genes were involved in cell cycle regulation, DNA replication, and epithelial–mesenchymal transition (EMT). Furthermore, C17orf75 expression was closely correlated with immune infiltration, ferroptosis-related genes, and m6A regulators. Knockdown of C17orf75 inhibited the proliferation, migration, and invasion of LIHC cells. C17orf75 knockdown induced G2-phase arrest without significantly affecting apoptosis. Moreover, knockdown of C17orf75 suppressed EMT. Conclusion C17orf75 plays an important role in LIHC progression by regulating cell cycle progression and EMT, and it may serve as a potential therapeutic target for LIHC.
Hao Liang, Nanbin Liu, Yibing Melody Zhai et al.· Frontiers in Immunology· 0 citations