2. Academic Validation
  3. CAF-derived exosomes promote the proliferation and invasion of pituitary adenoma cells via miR-184 transfer

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

  • Brain Res Bull. 2025 Dec 5:234:111678. doi: 10.1016/j.brainresbull.2025.111678.
Qiu Du 1,  Zhiyong Chen 2,  Weiyu Zhang 3,  Mengchao Zhu 4,  Zhichao Yang 4,  Yaru Li 5,  Lei Xu 5,  Jianmin Zhang 6,  Aijun Peng 7,  Qingling Feng 8
Affiliations

Affiliations

  • 1 Department of Neurosurgery, the Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou 225012, China; Department of Neurosurgery, the First People's Hospital of Guannan County, Lianyungang 223500, China; Department of Central Laboratory, the Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou 225012, China.
  • 2 Department of Neurosurgery, the First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510632, China.
  • 3 Center for Vascular Surgery and Interventional Oncology, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350001, China.
  • 4 Department of Neurosurgery, the First People's Hospital of Guannan County, Lianyungang 223500, China.
  • 5 Department of Central Laboratory, the Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou 225012, China.
  • 6 Department of Neurosurgery, the First People's Hospital of Guannan County, Lianyungang 223500, China. Electronic address: [email protected].
  • 7 Department of Neurosurgery, the Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou 225012, China; Department of Neurosurgery, the First People's Hospital of Guannan County, Lianyungang 223500, China. Electronic address: [email protected].
  • 8 Department of Emergency Intensive Care Unit, the Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou 225012, China. Electronic address: [email protected].
PMID: 41352438 DOI: 10.1016/j.brainresbull.2025.111678
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.

Keywords

Cancer-associated fibroblasts; Cell proliferation; Exosomes; MiR-184; Pituitary adenoma.

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