Gastric cancer is a common and high-incidence malignant gastro-intestinal cancer that seriously threatens human life. Evidence suggests that microRNAs (miRNAs) play an essential role in regulating the occurrence and development of gastric cancer, but the possible mechanisms and effects remain to be further explored. In the present study, a new tumour suppresser function of miR-484 was identified in gastric cancer. The expression of miR-484 was obviously decreased, and the expression of CCL-18 was obviously increased in gastric cancer tissues and cell lines. In addition, upregulation of miR-484 suppressed cell proliferation, migration and invasion, and induced cell cycle arrest in G1 phase and cell apoptosis in gastric cancer cells. Besides, miR-484 mimics could block the PI3K/AKT signalling pathway. Moreover, CCL-18 was confirmed as a direct target of miR-484 by binding its 3'-UTR, and over-expression of CCL-18 could restore the effects of miR-484 on the growth and metastasis of gastric cancer. Finally, in vivo experiments showed that over-expression of miR-484 inhibited the subcutaneous tumorigenicity of gastric cancer cells, and the inhibition was blocked after over-expression of CCL-18. To conclude, miR-484 expression was downregulated in gastric cancer tissues and cells and played an anti-cancer role in the occurrence and development of gastric cancer, which may be achieved by inhibiting the expression of transcription factor CCL-18 and blocking the PI3K/AKT pathway.
Keywords: CCL-18; PI3K/AKT signalling; gastric cancer; metastasis; microRNA-484; proliferation.
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