Integrative Bioinformatics and Experimental Validation Reveal that METTL9 Drives Lung Adenocarcinoma Progression via TGF-β/Smad-Mediated EMT Activation.

Transcriptomic network analysis and functional evidence identify a candidate EMT hub signature associated with nasopharyngeal carcinoma progression.

Prognostic significance of the TMPO-AS1/ hsa-let-7b-5p axis and nTreg infiltration in lung adenocarcinoma: an in silico analysis

While several G2/M oncogenes are known to promote tumor progression, their coordinated tumor-suppressive networks antagonizing this axis and their regulatory and immunological contexts remain poorly defined. We performed a multi-layered integrative analysis combining correlation profiling (UALCAN and ENCORI), multi-endpoint survival analysis (KM Plotter: OS, FPS, PPS across pan-lung, LUAD, and smoker cohorts), and transcriptomic refinement using TNMplot. A miRNA–mRNA regulatory network was constructed via miRNet, refined using UALCAN expression filtering, KM survival, and CancerMIRNome ROC analysis, followed by ENCORI-based miRNA–gene correlation. Direct miRNA–mRNA and lncRNA–miRNA binding affinities were assessed using IntaRNA. lncRNAs associated with the key miRNA were identified via Enrichr, filtered by expression, correlation, and survival, and validated by binding and gene correlation analyses. Finally, immune cell correlations were evaluated using GSCA, and an integrated ROC model was generated in R. We identified a high-confidence panel of six tumor suppressors (CBX7, CD81, CRY2, CYBRD1, NR3C2, REEP5) and six G2/M oncogenes (AURKA, AURKB, BUB1, FOXM1, MELK, TTK) based on correlation, survival, and TNMplot criteria. hsa-let-7b-5p emerged as a central regulatory miRNA (AUC = 0.89) positively correlated with tumor suppressors and predicted to bind all six oncogenes. TMPO-AS1 was identified as an oncogenic lncRNA antagonizing hsa-let-7b-5p via strong binding (–15.85 kcal/mol) and negative correlation with tumor suppressors. An integrated lncRNA-miRNA-mRNA ROC model achieved an AUC ≈ 0.97. Immune analysis revealed reciprocal patterns: tumor suppressors correlated with MAIT, NKT, and Tfh cells and inversely with exhausted cells and nTregs, whereas oncogenes showed the opposite trend with the same. This study defines a robust G2/M -associated regulatory framework in LUAD, characterized by reciprocal dysregulation of oncogenes and tumor suppressors and associated with the predicted TMPO-AS1–hsa-let-7b-5p regulatory network, which is linked to a less immunosuppressive tumor microenvironment, offering potential prognostic and therapeutic implications in LUAD.

TPD52 promotes breast cancer cell migration, invasion and proliferation via activation of the MAPK/ERK signaling pathway

Elevated TPD52 expression was associated with longer overall survival in specific subgroups, including the basal-like subtype, invasive lobular carcinoma, and N0/N1 stages, and a random forest-based diagnostic model demonstrated high accuracy across multiple datasets.

Identification of a metastasis-associated prognostic gene signature in osteosarcoma through integrated bioinformatics and functional analysis

Colorectal cancer molecular subtypes and prognostic models based on NET-related genes and oxidative stress-associated signaling

Colorectal cancer (CRC) exhibits marked molecular and microenvironmental heterogeneity, and the TNM staging system alone does not fully explain differences in prognosis or treatment response. Neutrophil extracellular traps (NETs) and oxidative stress participate in inflammatory remodeling, immune regulation, and tumor progression in CRC. However, transcriptomic studies integrating NET-related programs with oxidative stress-associated signaling for molecular stratification and prognostic modeling remain limited. Transcriptome and clinical data from TCGA-COADREAD (training set, 449 tumor and 39 normal samples) and GSE39582 (validation set, 566 tumor and 19 non-tumor samples) were analyzed. Candidate NET-related and oxidative stress-associated genes were collected from GeneCards, Gene Ontology, and published NETosis signatures, and were further restricted by differential expression analysis (|log2FC| > 0.585, adjusted P < .05) and univariate Cox analysis (P < .05). Consensus clustering, survival analysis, immune infiltration analysis, mutation analysis, and oncoPredict-based drug sensitivity modeling were performed. A multigene prognostic model was constructed using LASSO-Cox regression and evaluated in both cohorts. Two molecular subtypes were identified. C1 showed a better prognosis, higher tumor mutational burden, higher immune checkpoint and immunogenicity scores, and an immune-active phenotype. C2 showed poorer survival, enrichment of NET formation and inflammatory pathways, lower relative neutrophil infiltration by CIBERSORT, and predicted sensitivity to JAK, Wnt/β-catenin, proteasome, and cell-cycle checkpoint inhibitors. The prognostic model separated high- and low-risk patients in both the training and validation cohorts, with 1-, 3-, and 5-year area under the curves of 0.698, 0.711, and 0.645 in TCGA-COADREAD and 0.542, 0.578, and 0.569 in GSE39582. This study proposes NET-related CRC molecular subtypes with oxidative stress-associated biological context and develops a transcriptomic risk model with external validation. The findings suggest subtype-specific immune and therapeutic features, while prospective clinical and functional validation is required before clinical translation.

The miR-338-5p/METTL3 axis regulates m6A modification to inhibit tumor progression in triple-negative breast cancer.