Role of cancer‐associated fibroblast‐derived exosomal microRNAs in breast cancer progression: A systematic review
Matine Hajarian‐Rezazadeh, Fatemeh Fattahi, Mahmood Shekari‐Khaniani, Mehdi Khorrami, Akbar AmirfirouziAbstract
Background
Cancer‐associated fibroblasts (CAFs) are key components of the breast cancer tumor microenvironment and mediate communication with tumor cells through extracellular vesicles carrying microRNAs (miRNAs). These miRNAs may influence breast cancer progression by regulating oncogenic and tumor‐suppressive pathways.
Methods
This systematic review was conducted according to PRISMA guidelines. PubMed, Scopus, Web of Science, and Embase were searched for English‐language studies published up to July 2026. After duplicate removal and screening against predefined eligibility criteria, 18 studies were included. Data on study characteristics, CAF‐derived miRNAs, molecular targets, signaling pathways, and functional outcomes were extracted and qualitatively synthesized.
Results
CAF‐derived miRNAs were associated with multiple breast cancer‐related processes, including epithelial‐mesenchymal transition, cancer stem cell maintenance, metastasis, metabolic reprogramming, and therapeutic resistance. Tumor‐promoting miRNAs included miR‐92a, miR‐181d, miR‐221, miR‐3613‐3p, miR‐3960, and miR‐20, whereas miR‐16, miR‐148a, miR‐7641, miR‐4516, and miR‐1‐3p mainly showed tumor‐suppressive effects. Across studies, these miRNAs converged on pathways linked to increased invasiveness, phenotypic plasticity, and reduced response to therapy.
Conclusions
CAF‐derived exosomal miRNAs are important mediators of stromal‐tumor communication in breast cancer and may serve as promising biomarkers and therapeutic targets. However, heterogeneity among CAF subpopulations, variability in extracellular vesicle isolation methods, and limited clinical evidence highlight the need for standardized multicenter studies.