Bone marrow mesenchymal stem cell-derived exosomal miR-618-3p is associated with reduced proliferation and epithelial-mesenchymal transition markers in a chronic atrophic gastritis cell model: A preliminary in-vitro study.

Background

Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) can deliver microRNAs to recipient cells and modulate their functions; however, investigations into their molecular effects have frequently relied on surrogate cancer cell lines, whose relevance to benign CAG pathology remains uncertain and must be explicitly acknowledged.

Objectives

To explore whether BMSC-derived exosomal miR-618-3p influences proliferation, apoptosis and epithelial-mesenchymal transition (EMT).

Methods

Twelve CAG tissues and six normal gastric mucosa samples were obtained from the laboratory tissue bank. The human gastric adenocarcinoma cell line SGC-7901 was used as an in-vitro malignant surrogate for exploratory mechanistic evaluation, not as a model of benign CAG. BMSC-derived exosomes (BMSC-exo) were isolated by ultracentrifugation and characterized. CAG cells were treated with control exosomes or exosomes enriched with miR-618-3p mimic. miR-618-3p and TFF3 expression were detected by RT-qPCR and Western blot. Cell proliferation was assessed by CCK-8, apoptosis by caspase-3 activity and epithelial-mesenchymal transition (EMT) markers by RT-qPCR. A dual-luciferase reporter assay validated the interaction between miR-618-3p and the TFF3 3'UTR.

Results

miR-618-3p was decreased and TFF3 increased in CAG tissues (both p < 0.05). The dual-luciferase assay suggested a direct interaction between miR-618-3p and the TFF3 3'UTR. Unexpectedly, unmodified BMSC-exo treatment reduced miR-618-3p expression in recipient SGC-7901 cells, increased TFF3 protein levels, enhanced proliferation, reduced caspase-3 activity, decreased E-cadherin and increased vimentin expression (all p < 0.05. In contrast, BMSC-exo enriched with miR-618-3p mimic increased miR-618-3p levels, suppressed TFF3, reduced proliferation, increased caspase-3 activity, upregulated E-cadherin and downregulated vimentin (all p < 0.05).

Conclusion

In this preliminary in-vitro study using a gastric adenocarcinoma cell line, BMSC-exo miR-618-3p was associated with reduced TFF3 expression and altered proliferation, apoptosis and EMT markers. These findings describe a potential regulatory axis but remain strictly exploratory.