miR‐548d‐3p inhibits the invasion and migration of gastric cancer cells by targeting GKN1

Abstract

Background:The aim of this study was to explore the function and mechanism of GKN1 in gastric cancer (GC) progression.Methods: Firstly, we used GEO2R to perform differential gene analysis on GSE26942 and GSE79973 and constructed the protein-protein interaction network of differential genes by STRING. Next, the cytoHubba, Mcode plugins, and GEPIA were used to obtain our follow-up research object GKN1. Then, the function of GKN1 in GC was verified by scratch and transwell assay in GC cells. We further analyzed the genes related to GKN1 through LinkedOmics, and exported top 100 genes positively or negatively correlated with GKN1. Meanwhile, Metascape was performed on these genes.Finally, we analyzed the miRNAs that bind to GKN1 through the miRDB and verified the correlation between miR-548d-3p and GKN1 using dual-fluorescence and quantitative PCR experiments.Results: Bioinformatics analysis showed that there were 52 differential genes on GSE26942 and GSE79973. In addition, the results of functional assays indicated that overexpressed GKN1 can inhibit GC cell migration and invasion, while GKN1 knockdown demonstrated the opposite effect. Additionally, Metascape analysis results showed that the 3′-UTR region of mRNA is rich in AU sequences, based on which we infer that mRNA may be regulated by miRNA. Dual-fluorescence and quantitative PCR assays clarified that miR-548d-3p may be one of the target miRNAs of GKN1, which was up-regulated in GC tissues. Conclusions:In summary, we clarified that miR-548d-3p regulates GKN1 to participate in GC cell migration and invasion, and provides a possible target for the prognostic diagnosis and treatment of GC.

Clinical application and detection techniques of liquid biopsy in gastric cancer

“…In a recent meta-analysis, Xu et al [142] found that miR-21, miR-106, miR-421, and miR-223 have better diagnostic efficacy for GC, with miR-421 particularly useful as an auxiliary diagnostic indicator for GC; the AUC of its diagnostic GC can reach 0.92. More studies found that miR-548d-3p [153], miR-4742-5p [154], and miR-23b [145], which are significantly up-regulated in GC, and miR-137-3p [152], miR-148a [144], and miR-875-5p [143], which are significantly down-regulated in GC, are effective in distinguishing GC patients from healthy control individuals. In terms of metastasis, miR-17-5p and miR-4742-5p are up-regulated in GC.…”