Let-7i-3p inhibits the progression of gastric cancer by targeting CCND1 and suppressing the NF-κB signaling pathway.

Gastric cancer (GC) often presents as a malignant tumor of the human digestive system. Let-7i-3p has been confirmed to participate in the regulation of various cancers, while the biological mechanisms of Let-7i-3p in GC remains unknown. In this study, we investigated the role of let-7i-3p in GC. The effects of let-7i-3p on GC proliferation were determined by Cell Counting Kit-8 (CCK-8), colony formation and cell-cycle assays. The ability of migration was examined by transwell and wound-healing assay. Dual Luciferase reporter assay was used to validate the interaction of let-7i-3p with its target gene. The xenograft mouse models were conducted to investigate the effects of let-7i-3p in vivo. The results showed that let-7i-3p inhibited the proliferation, migration and EMT in vitro and suppressed GC growth in vivo. Cyclin D1 (CCND1) was confirmed to be the direct target of let-7i-3p. The effects of let-7i-3p were recovered by properly upregulating CCND1. Similarly, the effects of the let-7i-3p inhibitor were rescued by siCCND1. Furthermore, we found that let-7i-3p inhibited EMT and decreased the NF-κB signaling pathway through downregulating CCND1. In summary, let-7i-3p could suppress proliferation, migration, cell cycle, and EMT via NF-κB signaling pathways by downregulation of CCND1 in GC, which suggests a potential therapeutic target for GC.