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.
<b><i>Background:</i></b> Accumulating evidence indicates that microRNAs play a key role in tumor progression and prognosis. However, the overall biological role and clinical significance of microRNA-552 (miR-552) in the pathogenesis of gastric cancer (GC) remain unclear. <b><i>Methods:</i></b> miR-552 expression was measured in 122 pairs of cancerous and noncancerous tissues and cell lines by quantitative real-time polymerase chain reaction. The relationship between miR-552 and the clinical parameters of patients was analyzed by the χ<sup>2</sup> test; Kaplan-Meier analysis and multivariate Cox regression analysis were used to predict the overall survival time and prognosis of patients with different expression of miR-552. Finally, CCK-8 and Transwell were used to detect the changes in cell proliferation, migration, and invasion ability. <b><i>Results:</i></b> miR-552 was expressed at markedly high levels in GC tissues compared to normal tissues and in some GC cell lines (<i>p</i> < 0.001). The upregulation of miR-552 was significantly associated with tumors with advanced TNM stage (<i>p</i> = 0.026), lymph node metastasis (<i>p</i> = 0.018), intestinal metaplasia (<i>p</i> = 0.044), and genomically stable subtype (<i>p</i> = 0.035). Moreover, GC patients with high miR-552 expression showed shorter overall survival (log-rank test, <i>p</i> = 0.011) than those with low expression. Meanwhile, miR-552 was an independent prognostic factor for GC patients (HR 5.657, 95% CI 1.619–19.761, <i>p</i> = 0.007). Finally, miR-552 overexpression promoted the proliferation, migration, and invasion of GC cells (<i>p</i> < 0.01). <b><i>Conclusion:</i></b> Taken together, our results indicate that miR-552, as an oncogene of GC, can promote cell proliferation, migration, and invasion, and miR-552 may be a novel prognostic biomarker for GC.
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