miR-100-loaded liposomal nanoparticles inhibit migration and invasion of gastric cancer cells through targeting trefoil factor 1 to mediate stromal cell derived factor-1a/C-X-C chemokine receptor type 4 signaling pathway

Abstract

Abnormal expression of miR-100 is indicated to influence the progression of gastric cancer (GC). As a carrier of miR-100, liposomal nanoparticles (LNPs) can accelerate the entry of miR-100 into cells and improve drug effectiveness. In this study, we investigated the underlying mechanism whereby LNPs carrying miR-100 impact invasiveness of GC cells to provide a new strategy for managing the disorder. Human GC cells were treated with empty vectors, miR-100 mimic, and miR-100-loaded LNPs. SDF-1a/CXCR4 inhibitor was established as control group. Upon treatments, RT-qPCR was used to determine miR-100 expression in GC cells and Transwell and scratch assay was used to assess cell migration and invasion. Luciferase-reporter gene assay and Western blot analysis detected the interaction between miR-100 and SDF-1a/CXCR4 signaling pathway. Treatment with miR-100-loaded LNPs obtained the highest expression of miR-100, even higher than transfection with miR-100 mimic (P < 0.05), without difference between miR-100 mimic group and empty vector group (P > 0.05). With amplified bands of 610 bp detected in the miR-100-loaded LNPs, the nanoparticles dramatically decreased cell migration and invasion with the lowest number of migrated cells and migration speed and healing rate among all the groups. Empty vector and miR-10 mimic exerted similar effect on cell migration and invasion (P > 0.05). With binding regions between them, miR-100 was indicated as the target gene of TFF1. The fluorescence intensity of mutant plasmid was greater than that of wild-type plasmid (P < 0.05). Moreover, the miR-100-loaded LNPs resulted in decreased SDF-1a/CXCR4 expression, lower than that of the other groups. Isolated overexpression of miR-100 or empty vector similarly down-regulated SDF-1a/CXCR4.Collectively, the miR-100 loaded with LNPs effectively up-regulates miR-100 expression and inhibits GC cell progression through targeting TFF1 protein and regulating the SDF-1a/CXCR4 signaling pathway.