HOXA1 is a member of the Homeobox gene family, which encodes a group of highly conserved transcription factors that are important in embryonic development. However, it has been reported that HOXA1 exhibits oncogenic properties in many malignancies. This study focused on the expression and clinical significance of HOXA1 in gastric cancer (GC). To assess the mRNA and protein expression of HOXA1 and cyclin D1 in GC tissues, we utilized qRT-PCR and western blotting, respectively. The effects of HOXA1 on GC cell proliferation, migration, and invasion, as well as xenograft tumor formation and the cell cycle were investigated in our established stable HOXA1 knockdown GC cell lines. The protein expression of HOXA1 and cyclin D1 was examined by immunohistochemistry using GC tissue microarrays (TMA) to analyze their relationship on a histological level. The Kaplan-Meier method and cox proportional hazards model were used to analyze the relationship of HOXA1 and cyclin D1 expression with GC clinical outcomes. HOXA1 mRNA and protein expression were upregulated in GC tissues. Knockdown of HOXA1 in GC cells not only inhibited cell proliferation, migration, and invasion in vitro but also suppressed xenograft tumor formation in vivo. Moreover, HOXA1 knockdown induced changes in the cell cycle, and HOXA1 knockdown cells were arrested at the G1 phase, the number of cells in S phase was reduced, and the expression of cyclin D1 was decreased. In GC tissues, high cyclin D1 mRNA and protein expression were detected, and a significant correlation was found between the expression of HOXA1 and cyclin D1. Survival analysis indicated that HOXA1 and cyclin D1 expression were significantly associated with disease-free survival (DFS) and overall survival (OS). Interestingly, patients with tumors that were positive for HOXA1 and cyclin D1 expression showed worse prognosis. Multivariate analysis confirmed that the combination of HOXA1 and cyclin D1 was an independent prognostic indicator for OS and DFS. Our data show that HOXA1 plays a crucial role in GC development and clinical prognosis. HOXA1, alone or combination with cyclin D1, may serve as a novel prognostic biomarker for GC.

The interaction between tumour-associated neutrophils (TANs) and angiogenesis plays a crucial role in tumour progression. However, the specific regulatory mechanisms by which different TANs populations influence angiogenesis in colorectal cancer (CRC) remain poorly understood. The study integrates our own dataset with publicly available single-cell RNA sequencing (scRNA-seq) data to analyze the infiltration of various single-cell types in colorectal cancer (CRC). Using in vitro experiments, immunofluorescence, and animal models treated with anti-VEGFR antibodies, we investigated the role of tumor-associated neutrophils (TANs) in CRC and angiogenesis. We conducted RAB31 knockdown cell line, RNA sequencing, Western blotting, quantitative PCR, ELISA, tube formation assays, CCK8, and clonogenic assays, combined with in vivo experiments, to elucidate the impact of RAB31 in the tumor microenvironment (TME) and the mechanism by which tumor-derived RAB1 regulates TANs recruitment. Single-cell analysis revealed a significant infiltration of myeloid cells, particularly TANs, in CRC tumour tissue compared to normal tissue. RAB31 was found to be involved in malignant cell pathways, promoting CRC progression. Depletion of TANs substantially suppressed tumour growth and angiogenesis, while VEGFR blockade inhibited tumour growth and altered TANs infiltration in response to angiogenesis status. In vitro, knockdown of RAB31 expression inhibited tumour cell proliferation, and CXCL2 protein secretion was significantly reduced in shRab31-transfected tumour cells. In vivo, tumour tissue from shRab31 models showed decreased angiogenesis and reduced Neutrophil Extracellular Traps (NET) production, alongside reduced TANs infiltration. Moreover, CXCR4 expression was significantly elevated in TANs, and tumour cells influenced TANs through the CXCL2–CXCR4 axis. RAB31 regulated the PI3K–Akt signalling pathway, which is linked to neutrophil recruitment in CRC. Our findings suggest that tumour-derived RAB31 regulates the CXCL2–CXCR4 signalling pathway in CRC. RAB31 promotes CXCL2 secretion through the PI3K-Akt signalling pathway, facilitating TANs recruitment and angiogenesis, thereby driving tumour growth. This work enhances our understanding of the complex role of TANs and RAB31 in CRC progression and provides new insights into potential therapeutic strategies targeting the tumour microenvironment. The online version contains supplementary material available at 10.1186/s12967-026-07908-6.