TBX6 promotes proliferation, invasion, and migration in colorectal cancer: Integrated transcriptomic and protein interaction network analysis.

ZNF695 Promotes Colorectal Cancer Progression Through Transcriptional Activation of CBX8 and Subsequent Wnt/β-Catenin Signaling Activation.

In this investigation, we examined the functional mechanism of the transcription factor zinc finger protein 695 (ZNF695) and its target gene chromobox protein homolog 8 (CBX8) in colorectal cancer (CRC) migration and invasion. HCT-116 and LOVO cell lines were used to establish cell models with knocked-down ZNF695 and knocked-down or over-expressed CBX8. To comprehensively evaluate the functional contributions of ZNF695 and CBX8 to cellular phenotypes, we employed CCK-8, wound-healing, and Transwell assays to evaluate cell proliferation, migration, and invasion, respectively. To assess the impact of ZNF695 on tumor progression, we generated a xenograft model utilizing nude mice. A FLAG-ZNF695 expression plasmid was constructed, and ChIP-seq experiments were performed. By integrating mRNA sequencing data following ZNF695 knockdown with highly expressed genes in CRC from the TCGA database, CBX8 was identified as a putative downstream target of ZNF695. We employed a dual-luciferase reporter assay to validate the specific binding affinity of ZNF695 toward the CBX8 promoter region. To elucidate the specific biological cascades modulated by ZNF695 and CBX8, we conducted a comprehensive pathway enrichment analysis. Rescue experiments were conducted to determine whether the ZNF695/CBX8 regulatory axis upregulates the expression of the Wnt signaling pathway downstream targets, AXIN2 and CCND1. Both in vitro assays and in vivo models confirmed that silencing ZNF695 dramatically suppresses CRC cell proliferation, migration, and invasion, while concurrently impeding tumor progression. ChIP-seq coupled with dual-luciferase reporter assays substantiated the direct binding of ZNF695 to the CBX8 promoter. Furthermore, CBX8 depletion significantly attenuated the migratory and invasive phenotypes of CRC cells. Restoring CBX8 expression effectively rescued the migratory and invasive deficits in CRC cells induced by ZNF695 silencing. Re-expression of CBX8 in ZNF695-silenced cells restored Wnt/β-catenin signaling activity, accompanied by increased expression of AXIN2 and CCND1. ZNF695 promotes CRC progression by transcriptionally activating CBX8 and subsequently enhancing Wnt/β-catenin signaling, thereby promoting tumor cell proliferation, migration, and invasion.

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

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.

NTMT1 (METTL11A) promotes MYC-dependent proliferation and downstream HLA-A suppression in cervical cancer

Background Identifying upstream molecular regulators linking tumor proliferation with immune-related alterations remains an important challenge in cancer therapy. NTMT1 (METTL11A), a protein N-terminal methyltransferase, has been implicated in tumorigenesis; however, its role in coordinating tumor–immune interaction is poorly understood. Methods We performed integrative single-cell RNA sequencing (GSE208653) and spatial transcriptomics (GSE208654) analyses to characterize NTMT1 expression and function in cervical cancer. Spatial deconvolution and microenvironmental co-localization analyses were used to define context-specific effects. Functional validation was conducted using RT–qPCR, Western blotting, multiplex immunofluorescence, and flow cytometry-based assays. Results NTMT1 exhibited heterogeneous expression across epithelial and immune cell populations, with enrichment in squamous cell carcinoma. Spatial transcriptomics revealed that NTMT1-positive regions were associated with altered immune composition, including reduced macrophage and increased NK/T cell infiltration. In epithelial-enriched regions, NTMT1 expression correlated with activation of cell cycle pathways, including MYC, E2F1, CDK1, and CCNB1. Functional experiments demonstrated that NTMT1 promotes cell cycle progression via MYC upregulation. In epithelial–NK/T co-localization niches, NTMT1 was associated with modulation of antigen presentation pathways and suppression of HLA-A expression. Functionally, NTMT1 overexpression reduced IFN-γ production by CD8+ T cells under the co-culture conditions used in this study, which was partially restored by HLA-A re-expression. Conclusion NTMT1 was identified as a candidate regulator associated with MYC activation and HLA-A suppression. Although the precise molecular mechanism remains to be elucidated, functional experiments demonstrated that NTMT1 overexpression was accompanied by increased MYC expression, reduced HLA-A expression, enhanced cell-cycle progression, and impaired CD8+ T-cell function. These findings identify NTMT1 as a candidate regulatory node associated with MYC activation and downstream HLA-A suppression, warranting further mechanistic and in-vivo investigation, highlighting NTMT1 as a promising candidate for future therapeutic investigation. Further in vivo studies will be required to determine its suitability as a target for combination immunotherapy.

Cadherin-mediated cell adhesion networks drive tumor growth and therapeutic responses in head and neck cancer.

BACKGROUND Cadherin family genes (CDH1, CDH2, and CDH3) regulate cell-cell adhesion and epithelial integrity and have emerging roles in tumorigenesis. However, their molecular and functional relevance in Head and Neck Squamous Cell Carcinoma (HNSC) remains incompletely defined. METHODS Cadherin expression was evaluated in HNSC and normal oral epithelial cell lines using RT-qPCR. Multi-omics analyses of transcriptomic, methylation, mutation, and copy number variation (CNV) data were performed using TCGA datasets through GSCA, OncoDB, cBioPortal, and UALCAN. Prognostic significance was assessed using Kaplan-Meier and meta-analysis approaches. miRNA-mRNA interactions were predicted using miRNet and validated experimentally. Immune associations, drug sensitivity, and protein-protein interactions were explored using TISIDB, GSCA, STRING, and DAVID. Functional effects of CDH1 and CDH2 were evaluated by siRNA knockdown in FaDu and SCC9 cells, followed by proliferation, colony formation, wound healing, and xenograft assays. RESULTS CDH1, CDH2, and CDH3 were significantly upregulated in HNSC cell lines and TCGA tumor samples, with CDH3 showing the highest diagnostic accuracy (AUC = 0.90). Hypomethylation and CNV amplification contributed to cadherin dysregulation, particularly for CDH2 and CDH3. Elevated cadherin expression correlated with poor overall survival. miR-200a-3p and miR-200c-3p were identified as shared regulators. Cadherin expression also showed associations with immune modulators and drug response. Functionally, CDH1 and CDH2 knockdown suppressed proliferation, migration, and tumor growth. CONCLUSION Cadherin genes, particularly CDH3, show diagnostic and prognostic relevance in HNSC, while CDH1 and CDH2 contribute to tumor cell growth and migration. Further studies are required to determine their therapeutic potential.

YTHDF3 Promotes the Progression of Gastric Cancer by Activating the Wnt/β-Catenin Signaling Pathway via Targeting NEK7.

OBJECTIVE Gastric cancer remains a major global health burden. This study aimed to investigate the biological function, clinical significance, and underlying molecular mechanism of the RNA-binding protein YTHDF3 in gastric cancer (GC) progression. METHODS YTHDF3 expression was analyzed using public databases (TCGA, GEO), clinical GC specimens (IHC, RT-qPCR), and GC cell lines. Functional roles were assessed through in vitro proliferation, migration, invasion, and apoptosis assays following YTHDF3 knockdown or overexpression, and via an in vivo subcutaneous tumor model. Mechanistic insights were gained through RNA sequencing, RIP-qPCR, dual-luciferase reporter assay, co-immunofluorescence, rescue experiments, and western blotting to identify downstream targets and signaling pathways. RESULTS YTHDF3 was significantly upregulated in GC tissues, correlating with lymph node metastasis and advanced TNM stage. In vitro, YTHDF3 knockdown inhibited GC cell proliferation, migration, and invasion while promoting apoptosis, whereas its overexpression had the opposite effects. In vivo, YTHDF3 knockdown suppressed tumor growth. Mechanistically, YTHDF3 directly bound to and stabilized NEK7 mRNA. NEK7 was highly expressed in GC and crucial for YTHDF3-mediated oncogenic effects. Furthermore, YTHDF3 promoted GC progression by activating the Wnt/β-catenin signaling pathway via NEK7, which was validated using a pathway inhibitor (IWR-1-endo). CONCLUSION This study identifies the YTHDF3/NEK7 axis as a key regulator of GC progression via activation of the Wnt/β-catenin pathway. YTHDF3 represents a potential prognostic biomarker and a promising therapeutic target for GC.