Crocin inhibits the migration, invasion, and epithelial-mesenchymal transition of gastric cancer cells via miR-320/KLF5/HIF-1α signaling

Abstract

The biological activities of crocin, one of the main bioactive compounds of saffron, include anti-inflammatory, antioxidant, antidepressant, and anticancer effects. Crocin has been shown to trigger the apoptosis of gastric cancer cells, but its effect on the metastasis of gastric cancer cells remains unclear. Krüppel-like factor 5 (KLF5) and hypoxia-inducible factor-1α (HIF-1α) are important transcription factors in the development of gastric cancer. KLF5 and HIF-1α expression were analyzed in gastric cancer tissues and cells. Following exposure to crocin, AGS and HGC-27 gastric cancer cells were assessed with regard to migration, invasion, and epithelial-mesenchymal transition (EMT) as well as the expression of KLF5, HIF-1α, and microRNA-320 (miR-320). The miR-320/KLF5/HIF-1α signaling pathway became the focus for further investigation of the mechanism of crocin in gastric cancer cell migration, invasion, and EMT. KLF5 and HIF-1α expression were elevated in gastric cancer tissues and cells, and KLF5 expression was positively correlated with the HIF-1α level in gastric cancer tissues. Crocin was associated with reduced expression of KLF5 and HIF-1α, whereas miR-320 expression was increased. Crocin also inhibited the migration, invasion, and EMT of gastric cancer cells. Upregulation of KLF5 attenuated crocin's function and elevated HIF-1α expression. Dual-luciferase reporter assay demonstrated that KLF5 was a target gene of miR-320. Crocin modulated KLF5 expression via elevation of miR-320 expression. In conclusion, crocin inhibits the EMT, migration, and invasion of gastric cancer cells, and this activity is mediated through miR-320/KLF5/HIF-1α signaling.

Keywords: crocin; epithelial-mesenchymal transition; gastric cancer; metastasis; miR-320/KLF5/HIF-1α.