Identification of the complex regulatory relationships related to gastric cancer from lncRNA-miRNA-mRNA network.

The oncogenesis and progression of gastric cancer are closely correlated with the complex regulatory relationships among messenger RNA (mRNA), long noncoding RNA (lncRNA), and microRNA (miRNA). After constructing the gastric cancer lncRNA-miRNA-mRNA regulatory network, we analyzed the network topology properties and found that lncRNA ADAMTS9-AS2 and C20orf166-AS1 and miRNA hsa-mir-204 are key nodes. Further functional enrichment analysis and survival analysis were performed on these key nodes and the RNAs interacting with them. We found that CHRM2, ANGPT2, and COL1A1 interacting with ADAMTS9-AS2 are enriched in the PI3K-Akt signaling pathway, and low expression of the ADAMTS9-AS2 is closely related to the prognosis of patients. Abnormal expression of CACNA1H, FLNA, and FLNC interacting with lncRNA C20orf166-AS1 is associated with MAPK signaling pathway in gastric cancer. In addition, the downregulated miRNA hsa-mir-204 promotes invasion and proliferation of gastric cancer cells by regulating the abnormal expression of mRNAs (CHRDL1 and NPTX1) and lncRNAs (ADAMTS9-AS2, NKX2-1-AS1, TLR8-AS1, and VCAN-AS1). This study systematically analyzed the lncRNA-miRNA-mRNA regulatory network of gastric cancer, which not only has a new understanding of the pathogenesis of gastric cancer, but also provides new insights for the early diagnosis and treatment of gastric cancer.