miR-27b-3p Inhibits Invasion, Migration and Epithelial-mesenchymal Transition in Gastric Cancer by Targeting RUNX1 and Activation of the Hippo Signaling Pathway

Abstract

Background: Gastric cancer (GC) accounts for high mortality, which seriously threatens people’s health. This study set out to probe into the effect and mechanism of miR-27b-3p on invasion and migration of GC. Methods: The miRNA sequence data of GC was acquired from The Cancer Genome Atlas (TCGA) database. The differential expression of miRNAs (DEMis) was acquired through R packages “edgeR” and “limma.” TargetScan, picTar, RNA22, PITA, and miRanda were performed to predict the target gene of miR-27b-3p. Western-blot and RT-PCR were applied to detect the expression level of the selected candidate. Transwell assays evaluated the effect of miR-27b-3p and runt-related transcription factor 1 (RUNX1) on cell migration and invasion. The rescue assay was achieved by co-culture with mimics of miR-27b-3p and vector of RUNX1. The psiCHECK2 vector was used in the luciferase report assay. Results: We found miR-27b-3p was down-regulated in GC and associated with GC patients' poor survival based on the TCGA data and bioinformatics analysis. Furthermore, RUNX1 was the target gene of miR-27b-3p, which was proved by the luciferase report assay. miR-27b-3p and RUNX1 jointly participate in the regulation of the Hippo pathway. The up-regulated miR-27b-3p could inhibit epithelial–mesenchymal transition (EMT) as well as invasion and migration. However, an overexpressed RUNX1 could weaken this phenomenon. Conclusion: miR-27b-3p was down-regulated in GC, and it could regulate the Hippo pathway and affect EMT by inhibiting RUNX1 expression.