Human umbilical cord mesenchymal stem cell-derived exosomes inhibit migration and invasion of breast cancer cells via miR-21-5p/ZNF367 pathway.

Background: Human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-exos) exhibit various roles in breast cancer development. The molecular mechanisms underlying hucMSC-exos in breast cancer cells are not fully clear. In the current study, we set out to investigate the downstream signaling pathways of hucMSC-exos in MCF-7 cells, a commonly used cell line to study breast cancer.

Methods: hucMSC-exos' effects on MCF-7 cells were examined using immunocytochemistry. An inhibitor and a mimic of miR-21-5p were administered. The mRNA and protein levels of ZNF367 were analyzed using real-time quantitative reverse transcription PCR (qRT-PCR)and western blotting. Transwell assays were used to measure invasion and migration. Dual-luciferase assays were performed to investigate the binding sites between miR-21-5p and ZNF367. To manipulate expression, an overexpressing of ZNF367 approach was utilized.

Results: We confirmed that hucMSC-exos can be internalized by MCF-7 cells. hucMSC-exos dramatically inhibited migration and invasion behaviors through downregulation of ZNF367 and upregulation of miR-21-5p. miR-21-5p directly binds on 3'UTR of ZNF367. miR-21-5p mimic partially abolished overexpressed ZNF367-induced migration and invasion. In breast cancer tissues, there was a negative correlation between miR-21-5p and ZNF367 levels. The similar results were also obtained in human breast cancer MDA-MB-231 cells.

Conclusion: husMSC-exos are anti-oncogenic in MCS-7 cells. husMSC-exos suppress ZNF367 expression and promote miR-21-5p expression. miR-21-5p opposes ZNF367's actions during breast cancer development. miR-21-5p direct binds ZNF367 3'UTR to inhibit ZNF367 expression. The interaction between miR-21-5p and ZNF367 may serve as a future therapeutic approach to improve breast cancer prognosis.