Gastric cancer is a heterogeneous disease accompanied by the alteration of various causative genes. The discovery of molecular targets and potential mechanisms of gastric cancer is valuable. Here we explored the biological 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 proliferation, 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 proliferation, 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.

CPNE1

Gastric cancer

Proliferation

Apoptosis

MAPK pathway

RT-qPCR

DEGs

DAPI

Data will be made available on request.

© 2022 The Authors. Published by Elsevier B.V.