Exosome miR-3184-5p inhibits gastric cancer growth by targeting XBP1 to regulate the AKT, STAT3, and IRE1 signalling pathways.

Abstract

MicroRNAs can regulate the transcription of protein-coding genes associated with the development and progression of cancer. In this study, we explored the potential diagnostic function of exosome miR-3184-5p in gastric cancer. This exosome was isolated from the blood samples of 150 patients with gastric cancer and 60 healthy participants. The mean particle size and concentration of serum exosome in the patients with gastric cancer were 104.6 nm (93.97-115.84) and 6.21e+009 particles/ml (5.15e+009-7.12e+009), respectively. miR-3184-5p expression was substantially downregulated in the patients with gastric cancer compared with that in the healthy participants. The gastric cancer cell line HGC-27 was cultured and transfected with the mimic and an inhibitor to overexpress and inhibit miR-3184-5p expression. miR-3184-5p strongly suppressed cell proliferation, migration, and invasion but induced cell apoptosis. Luciferase reporter assay revealed that XBP1 was the target of miR-3184-5p. miR-3184-5p substantially downregulated the expression of CD44, cyclin D1, MMP2, p65, p-AKT, and p-STAT3 but upregulated that of GRP78, IRE1, p-JNK, and CHOP. Moreover, miR-3184-5p cleaved caspase-12 and inhibited BCL-2 expression. These results suggested that the downregulation of miR-3184-5p in patients with gastric cancer might regulate the AKT, STAT3, and IRE1 pathways to promote the vitality of gastric cancer cells.