CAF-derived exosomes promote the proliferation and invasion of pituitary adenoma cells via miR-184 transfer

Abstract

Pituitary adenomas (PAs) are common intracranial tumors whose mass effects and endocrine dysfunction pose serious threats to patient health. However, the mechanisms underlying their progression, particularly the role of the tumor microenvironment (TME), remain insufficiently studied. Within this context, cancer-associated fibroblasts (CAFs) have been shown to drive tumor development via extracellular matrix remodeling and extracellular vesicle release, but their specific contributions to PA progression remain unclear. In this study, we observed a correlation between PA invasiveness and fibroblast density in the TME. Functionally, both CAFs and CAF-derived exosomes significantly enhanced the proliferation and invasion of PA cells compared to normal fibroblasts. Small RNA sequencing identified 16 upregulated and 8 downregulated miRNAs in CAF-derived exosomes, with KEGG analysis indicating enrichment in MAPK signaling, regulation of actin cytoskeleton, and lysosome-related pathways. Among these, miR-184 was notably upregulated in both CAF-derived exosomes and PA specimens. We further demonstrated that exosomal miR-184 from CAFs could be transferred into PA cells, promoting their proliferation and invasion, while miR-184 knockdown attenuated the tumor-promoting effects of CAF-derived exosomes. Mechanistically, TLE1 was validated as a direct functional target of miR-184. In summary, our study reveals exosomal miR-184 as a key mediator of CAF-driven PA progression, highlighting its potential as a therapeutic target for PAs.