In summary, by combining differential networking information and molecular cell experiments verification, we generated and verified the testable hypotheses on the dysregulation mechanisms of GC around the crucial TFs and their top ranked DRLs, and proposed a CREB1/TCEAL2-MBNL1 signaling model, where TCEAL2 and MBNL1 were proved to be differentially regulated by CREB1 during tumorigenesis of gastric cancer. The gene discussed is CREB1; the disease is gastric cancer.