Modulation of tumor-derived exosomes and reprogramming of cancer-associated fibroblasts for colorectal cancer therapy

This study investigates whether and how CRC-derived hypoxic exosomes regulate NAF-to-CAF activation and promote angiogenesis via the lncRNA/miRNA axis. We propose that HIF1A-AS2 modulates tumor exosome function and fibroblast phenotype through the miR-33/HIF-1α axis in CRC. This hypothesis is supported by multiple machine learning algorithms, clinical data, molecular and genomic analyses, functional status profiling, drug response evaluation, trajectory inference, and cell–cell communication studies using bulk multi-omics and single-cell datasets (pan-cancer and in-house), as well as experimental validation.