Construction and characterization of rectal cancer-related lncRNA-mRNA ceRNA network reveals prognostic biomarkers in rectal cancer

Rectal cancer is an important cause of cancer-related deaths worldwide. In this study, the differentially expressed (DE) lncRNAs/mRNAs were first identified and the correlation level between DE lncRNAs and mRNAs were calculated. The results showed that genes of highly correlated lncRNA-mRNA pairs presented strong prognosis effects, such as GPM6A, METTL24, SCN7A, HAND2-AS1 and PDZRN4. Then, the rectal cancer-related lncRNA-mRNA network was constructed based on the ceRNA theory. Topological analysis of the network revealed that the network was maintained by hub nodes and a hub subnetwork was constructed, including the hub lncRNA MIR143HG and MBNL1-SA1. Further analysis indicated that the hub subnetwork was highly related to cancer pathways, such as 'Focal adhesion' and 'Wnt signalling pathway'. Hub subnetwork also had significant prognosis capability. A closed lncRNA-mRNA module was identified by bilateral network clustering. Genes in modules also showed high prognosis effects. Finally, a core lncRNA-TF crosstalk network was identified to uncover the crosstalk and regulatory mechanisms of lncRNAs and TFs by integrating ceRNA crosstalks and TF binding affinities. Some core genes, such as MEIS1, GLI3 and HAND2-AS1 were considered as the key regulators in tumourigenesis. Based on the authors' comprehensive analysis, all these lncRNA-mRNA crosstalks provided promising clues for biological prognosis of rectal cancer.