ArticleJournal of translational medicine2025
Multi-omics analyses identify mannose phosphate isomerase-centered hypoxia-induced angiogenesis signature in colorectal cancer.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
- Vulnerable plaques in atherosclerosis: focus on angiogenesis-associated phenotypic crosstalk.Frontiers in pharmacology · 2025Review
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Authors and funding
13 authors.
Funding
Abstract
backgroundHypoxia and angiogenesis are crucial hallmarks of cancer that play key roles in the development and progression of colorectal cancer (CRC). However, the transcriptional mechanism underlying hypoxia induced angiogenesis (HIA) remain elusive. This study aimed to explore the regulatory networks, molecular mechanisms, and prognostic value of HIA-related genes.
methodsWe collected multi-omics data, including chromatin immunoprecipitation sequencing (ChIP-seq), bulk RNA-seq, single cell RNA-seq, spatial transcriptomics, and microarray data from CRC patients and cell lines. Computational methods, including single sample gene set enrichment analysis (ssGSEA), signature-related gene analysis (SRGA), consensus clustering, and others, were utilized to explore the correlation between hypoxia and angiogenesis, identify the HIA-related genes, and establish the risk scoring system based on HIA-related genes. The role of mannose phosphate isomerase (MPI) was validated using quantitative real-time PCR (RT-qPCR), Co-immunoprecipitation (Co-IP), western blot, colony formation, tube formation assay, and subcutaneous xenograft tumor models in vitro and in vivo.
resultsWe identified 12 HIA-related genes that are transcriptionally activated by hypoxia-inducible factors (HIFs) and functionally implicated in angiogenesis in CRC. Based on the differentially expressed genes among HIA-related CRC subtypes, we constructed a prognostic scoring system termed HIAscore. Patients with high HIAscore was correlated with poor survival, aggressive phenotype, and immunosuppressive tumor microenvironment. Spatial analysis revealed sequestration regions between epithelial cells with higher HIAscore and T/I/NK cells, hindering their infiltration. Particularly, MPI was found to interact with lactate dehydrogenase A (LDHA), and promote proliferation and angiogenesis of CRC through phosphorylation and activation of Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) signaling pathways.
conclusionsThis study depicts the transcriptional landscape linking hypoxia and angiogenesis in CRC, and identifies MPI as a novel regulator of this process.
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