Figure 7.

Proposed scheme for the roles of miR-15a-3p, miR-16-1-3p, Twist1, Bcl2 and other EMT related genes in tumor invasion and metastasis. The down-regulated mature miR-15a-3p and miR-16-1-3p negatively regulate Twist1 expression. The up-regulated Twist1 would quickly induce the expression of N-cadherin, α-SMA and Fibronectin and so on. Together these genes promote the EMT process in GC and change the microenvironment to promote tumor invasion and metastasis. On the other hand, miR-15a-3p and miR-16-1-3p negatively regulate the expression of anti-apoptotic gene Bcl2 ⁴⁷. The up-regulated Bcl2 would suppress GC cell apoptosis to promote tumor development. In addition in a previous study ⁴⁹, Bcl2 could co-express with Twist1, therefore promote metastasis and inducing vasculogenic mimicry.