CPNE1 silencing inhibits cell proliferation and accelerates apoptosis in human gastric cancer

Gastric cancer is a heterogeneous disease accompanied by the alteration of various causative genes. The dis-covery of molecular targets and potential mechanisms of gastric cancer is valuable. Here we explored the bio-logical function of CPNE1 and its molecular mechanisms in gastric cancer. Immunohistochemistry and Kaplan-Meier plotter database were used to identify that CPNE1 was upregulated in human gastric cancer and high expression of CPNE1 suggested a worse prognosis. Silencing CPNE1 could effectively suppress tumor pro-liferation, accelerate cell apoptosis and arrest cell cycle in vitro. CPNE1 knockdown mediating apoptosis by PARP-1 cleavage via caspase-3 and-7 activation through cytochrome c release from mitochondria in gastric cancer cells. Xenograft mouse model showed that targeted inhibition of CPNE1 slowed down the rate of tumor growth in vivo. We also verified that CPNE1 knockdown inhibited the activation of MAPK pathway mediated by DDIT3-FOS-MKNK2 axis. Specific inhibitor of DDIT3-FOS-MKNK2 axis could suppress gastric cancer cell pro-liferation, concomitant with knockdown of CPNE1. In conclusion, CPNE1 silencing inhibited gastric cancer growth via deactivating DDIT3-FOS-MKNK2 axis, which indicated that CPNE1 might serve as a therapeutic target for gastric cancer.

Automated summary

CPNE1 is upregulated in gastric cancer and its high expression is associated with poor prognosis. Silencing CPNE1 inhibits tumor proliferation and induces cell apoptosis. CPNE1 knockdown deactivates the DDIT3-FOS-MKNK2 axis, leading to inhibition of the MAPK pathway and suppression of gastric cancer growth.