COL5A1 Promotes the Progression of Gastric Cancer by Acting as a ceRNA of miR-137-3p to Upregulate FSTL1 Expression

SIMPLE SUMMARY: The expression of a variety of microRNAs (miRNAs) and their target genes in gastric cancer is dysregulated and affects the progression of gastric cancer but has not been fully clarified, while bioinformatics is expected to become a method to reveal the relationship and function between them. Thus, through a variety of bioinformatics analyses and experiments, we confirmed that miR-137-3p played a tumor-suppressive role in gastric cancer, and its target gene COL5A1 could reversely sponge miR-137-3p to relieve its targeted inhibition of FSTL1, which may promote the progression of gastric cancer by affecting immune infiltration. These results may provide new ideas for the treatment and future research of gastric cancer. ABSTRACT: MicroRNAs (miRNAs) and their target genes have been shown to play an important role in gastric cancer but have not been fully clarified. Therefore, our goal was to identify the key miRNA–mRNA regulatory network in gastric cancer by utilizing a variety of bioinformatics analyses and experiments. A total of 242 miRNAs and 1080 genes were screened from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. Then, survival-related differentially expressed miRNAs and their differentially expressed target genes were screened. Twenty hub genes were identified from their protein–protein interaction network. After weighted gene co-expression network analysis was conducted, we selected miR-137-3p and its target gene, COL5A1, for further research. We found that miR-137-3p was significantly downregulated and that overexpression of miR-137-3p suppressed the proliferation, invasion, and migration of gastric cancer cells. Furthermore, we found that its target gene, COL5A1, could regulate the expression of another hub gene, FSTL1, by sponging miR-137-3p, which was confirmed by dual-luciferase reporter assays. Knockdown of COL5A1 inhibited the proliferation, invasion, and migration of gastric cancer cells, which could be rescued by the miR-137-3p inhibitor or overexpression of FSTL1. Ultimately, bioinformatics analyses showed that the expression of FSTL1 was highly correlated with immune infiltration.