Abstract
Accumulating studies indicate that circular RNAs (circRNAs) play critical roles in cancer progression. Most of them have been reported to act as microRNA sponges or interact with RNA-binding proteins; however, their full range of functions remains largely unclear. Recently, an increasing number of circRNAs have been found to encode proteins. C-E-Cad, a protein encoded by circular E-cadherin (circ-E-Cad), has been shown to have a great influence in the progression of glioblastoma, but its specific role in gastric cancer (GC) is unclear. Here, we found that both circ-E-Cad and C-E-Cad were upregulated in GC cell lines and GC tissues compared with a human gastric epithelial cell line (GES-1) and normal tissues. Knockdown of circ-E-Cad suppressed GC cell line proliferation and metastasis in vitro and in vivo, whereas overexpression of C-E-Cad had the opposite effects. Immunoblotting revealed that C-E-Cad exerted tumor-promoting functions by regulating the PI3K/AKT pathway. A rescue experiment showed that C-E-Cad but not circ-E-Cad was the executor of protumor biological functions. In addition, we demonstrated that the C-E-Cad expression level could have been increased by the TGF-β/Smad pathway. In summary, our results indicated that the TGF-β/Smad pathway could increase the expression of C-E-Cad to regulate GC cell proliferation, migration, and epithelial-mesenchymal transition by affecting PI3K/AKT signaling.