CircNR3C1 Alleviates Gastric Cancer Development by Inactivating AKT/mTOR.

Abstract

Differential level and regulatory effect of circNR3C1 in gastric cancer (GC) were determined. The differential levels of circNR3C1 in clinical samples of GC were determined. The association of circNR3C1 level with pathological indicators of GC was analyzed. After intervening circNR3C1 levels in gastric cancer cells, proliferative and migratory changes were investigated. Furthermore, we measured AKT and mTOR protein levels in GC cells intervened by circNR3C1. Finally, the role of AKT/mTOR in GC cell phenotypes regulated by circNR3C1 was explored. circNR3C1 was markedly lowly expressed in GC cells and tissues. A low level of circNR3C1 predicted high incidences of lymphatic or distant metastasis of GC. Knockdown of circNR3C1 enhanced proliferation and migration abilities in BGC-823 cells, whereas overexpression of circNR3C1 yielded the opposite results in AGS cells. circNR3C1 downregulated mTOR and AKT in GC cells. In addition, induction of the AKT activator could reverse the attenuated proliferative and migratory potentials in GC cells overexpressing circNR3C1. On the contrary, induction of the AKT inhibitor reversed the stimulated malignant phenotypes of GC with circNR3C1 knockdown. circNR3C1 inhibits GC to proliferate and migrate by inactivating the AKT/mTOR signaling. It is also closely linked to GC metastasis.