Effect of targeted regulation of miR-499a-5p/integrin β1 by circ_001567 on malignant progression of gastric cancer cells.

To investigate the effect of targeted regulation of miR-499a-5p/integrin β1 (ITGB1) by circ_001567 on malignant progression of gastric cancer cells. CircRNA expression and circRNA localization in gastric cancer were screened. The expression levels of circ_001567, miR-499a-5p and ITGB1 proteins in gastric cancer tissues and cells were detected by RT-qPCR and Western blot. Dual luciferase reporter assay was used to detect the targeting relationship between circ_001567 and miR-499a-5p and miR-499a-5p and ITGB1. HGC-27 cells were divided into si-NC group, si-circ_001567 group, miR-NC group, miR-499a-5p group, si-circ_001567 + anti-miR-499a-5p group, miR-499a-5p + vector group, miR-499a-5p + ITGB1 group. The expression levels of circ_001567 and miR-499a-5p were detected by RT-qPCR. CCK8 was used to detect cell proliferation. Transwell was used to detect cell migration and invasion. The expressions levels of ITGB1, Ki67, PCNA and MMP2 were detected by Western blot. Compared to adjacent tissues, the levels of circ_001567, circ_0002874, circ_0000437, circ_0001479, and circ_0101504 were significantly elevated in gastric cancer tissues; however, no significant difference was observed for circ_0072995. The expression variation of circ_001567 was the most pronounced among these circular RNAs. Notably, circ_001567 exhibited stability and was predominantly localized in the cytoplasm. In comparison with paracancerous tissues and GES-1 cells, both circ_001567 and ITGB1 protein levels were significantly increased in gastric cancer tissues and cell lines (MKN-28, HGC-27, SNU-1), while miR-499a-5p expression showed a marked decrease (P < 0.05). Knockout of circ_001567 or overexpression of miR-499a-5p resulted in reduced activity of gastric cancer cells as well as diminished numbers of migratory and invasive cells; additionally, there was a decrease in the expression levels of Ki67, PCNA, and MMP2 proteins (P < 0.05). Circ_001567 directly targeted miR-499a-5p and inhibited its function to mitigate the effects associated with the knockout of circ_001567 on proliferation, migration, and invasion within gastric cancer cells. Furthermore, miR-499a-5p regulated ITGB1 by targeting it directly; this upregulation counteracted the impacts that overexpression of miR-499a-5p had on cellular proliferation, migration, and invasion. The circ_001567/miR-499a-5p/ITGB1 axis represents a novel therapeutic target for gastric cancer. Our findings provide a mechanistic basis for targeted interventions, such as circRNA silencing or miRNA replacement therapies, to suppress tumor progression.