Exosomal circ0000549 promotes MNNG‑induced gastric cancer through miR‑15b‑5p/KIF1B

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Accumulating evidence indicates that environmental exposures, particularly to nitrites, play a critical role in the initiation and progression of gastric cancer (GC). During carcinogenesis, exosomes act as key mediators of intercellular communication. Exosomes derived from N‑methyl-N'‑nitro‑N‑nitrosoguanidine (MNNG)‑induced malignantly transformed GES‑1 cells (TGES‑1), as well as serum exosomes from gastric cancer patients with a history of high nitrite exposure, were found to influence normal cells and promote GC initiation. The present study established a malignant transformation model and applied bioinformatics analyses to screen and validate candidate circRNAs. A series of functional and mechanistic experiments were performed to elucidate the regulatory role of exosomes in GC progression. Circ0000549 was markedly upregulated in MNNG‑exposed GES‑1 cells, their derived exosomes and serum exosomes from patients with GC. Further investigations revealed that circ0000549 overexpression enhanced GES‑1 cell malignant features, while also modulating epithelial‑mesenchymal transition and stemness‑related properties. Nude mouse experiments demonstrated that circ0000549, carried by malignantly transformed exosomes, plays a crucial role in MNNG‑induced gastric carcinogenesis. Mechanistically, miR‑15b‑5p was identified as a potential target of circ0000549. Circ0000549 functioned as a sponge for miR‑15b‑5p, leading to increased KIF1B expression and subsequent activation of the PI3K/AKT signaling pathway. Collectively, these findings reveal that exosomal circ0000549 promotes malignant transformation of GES‑1 cells through the miR‑15b‑5p/KIF1B/PI3K/AKT axis. Exosomal circ0000549 may serve as a promising biomarker for GC diagnosis and prognosis, highlighting its potential as a target for future therapeutic investigation.

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