Targeted regulation of miR-17-5p on TMOD1 promotes the development of cardia cancer

Cardia cancer is a common type of gastric cancer. Most clinical prevention and prognosis focus on surgical resection, but the efficacy is not satisfactory. Studying the molecular mechanism of pathogenesis of cardia cancer helps us intervene in prognosis and treatment.

a total of 134 normal cases related to cardia cancer and 62 cases of cardia cancer samples from the Gene Expression Omnibus (GEO) database were collected. A series of bioinformatics analyses, including differential gene analysis, co-expression analysis, enrichment analysis, regulator prediction, and (Protein-protein interaction) PPI analysis validation were performed.

Differential analysis highlighted 10882 differential genes (p<0.05). Weighted gene co-expression network analysis indicated 6 functional disorder modules. TMOD1, JAM2, SPARC, ST18, NOS1 were key genes of each module. Enrichment analysis showed the dysfunctional module genes were mainly related to the proteinaceous extracellular matrix and neuroactive ligand-receptor interaction. Pivotal analysis of ncRNA demonstrated miR-17-5p significantly regulates modular genes including m1, m3, and m5. Target genes were backtracked according to the key regulators. Then, the Module_target gene_ncRNA interaction network diagram was constructed. The network shows m1 has the strongest regulation effect in the network. PPI showed that the core gene TMOD1 (Tropomodulin1) of m1 was at TOP10 in the algorithm. In other words, PPI indicated the importance of TMOD1 in the interaction network.

We believe that targeted regulation of miR-17-5p on TMOD1 gene affects the neuroactive ligand-receptor interaction pathway, and it promotes proliferation and apoptosis of cardia cancer cells.