Abstract
Background and Objectives: To screen key miRNAs and their target genes related to Toll-like receptor (TLR) activation in gastric cancer (GC) cells and analyze them bioinformatically. Materials and Methods: Venn diagrams were obtained to screen miRNAs that were upregulated/downregulated in both GSE54129 and GSE164174. The miRTarBase database was used to predict the target genes of upregulated miRNAs. The differentially expressed genes in the regulatory network were analyzed. miR-16-5p expression in different tissue samples and the variations in the methylation states of four hub genes were measured. Results: We found that GSE54129 included 21 normal gastric tissues and 111 gastric cancer tissues, GSE164174 included 1417 normal gastric tissues and 1423 gastric cancer tissues. Venn diagram analysis results showed that compared with the control group, a total of 68 DEmiRNAs were upregulated in the GSE54129 and GSE164174 datasets, and no common downregulated DEmiRNAs were found. On further analysis of the GSE108345 dataset, we obtained the competing endogenous RNA (ceRNA) network associated with the activation of TLRs, and listed the top 10 lncRNA-miRNA-mRNA networks, including 10 miRNAs, 86 mRNA and 134 lncRNAs. Cytological HuBBA scores yielded a total of 1 miRNA, 16 mRNAs and 45 lncRNAs, of which miR-16-5p scored the highest as it was considered a key miRNA for TLR activation in GC cells, which are important in response against microorganisms. The results of Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that endocytosis, microRNAs in cancer and the PI3K-Akt signaling pathway are related to TLR signaling. The results of in vivo experiments indicated that miR-16-5p was highly expressed in gastric cancer cells and tissues. Conclusions: Hsa-miR-16-5p's target genes mainly play a role by regulating the expression of four genes-MCL1, AP2B1, LAMB1, and RAB11FIP2. The findings provide a scientific basis for the development of immunotherapy for GC.