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

Abstract: 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.