Circ‐E‐Cad encodes a protein that promotes the proliferation and migration of gastric cancer via the TGF‐β/Smad/C‐E‐Cad/PI3K/AKT pathway

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.