Endogenous and Extracellular Roles of a Tumor Suppressor miR-379-5p in Gastric Cancer.

INTRODUCTION

MiRNAs play important roles in development of various cancers including gastric cancer. Exosomes are extracellular vesicles for translocating molecules. This study aimed to investigate the tumor suppressive roles of miR-379-5p in gastric cancer and to investigate the roles of exosomes in transporting miR-379-5p from intracellular to extracellular.

METHODS

Fifty-three pairs of gastric cancer and non-tumor tissue samples were collected. Five cell lines were applied. Functional assays including cell proliferation, cell migration and invasion, and cell adhesion assay were performed. Targets of miR-379-5p were screened and validated by Western blot. Expressions of endogenous miR-379-5p in gastric cancer cells and exosomal miR-379-5p in cell culture medium were evaluated by RT-qPCR. Medium of culturing AGS or BCG23 was applied for culturing MKN45 and HEK293T.

RESULTS

The results indicated that miR-379-5p was significantly downregulated in gastric cancer tissue samples and cell lines. Enforced expression of miR-379-5p inhibited gastric cancer cell proliferation, migration, and invasion, while miR-379-5p mimic enhanced cell adhesion to extracellular matrix. IGF1R was a potential target of miR-379-5p in gastric cancer. Expression of miR-379-5p was dramatically higher in exosomes in cell culture medium than its endogenous expression. Exosomes from cell culture medium of AGS or BCG23 could regulate endogenous expression of miR-379-5p in HEK293T cells.

CONCLUSIONS

MiR-379-5p was significantly downregulated and it functioned as a tumor suppressor in gastric cancer. MiR-379-5p was highly expressed in exosomes of culture medium than its endogenous expression. MiR-379-5p could be translocated from cells into cell culture medium and entered certain cell types via exosomes.