CPNE3 promotes colorectal cancer progression by regulating KIF4-mediated autophagy

Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. This study examines the role of CPNE3 in CRC progression and its interaction with KIF4 to identify potential therapeutic targets.

We identified CPNE3 as a candidate oncogene using bioinformatics. Its expression was measured by quantitative real-time polymerase chain reaction (qRT-PCR) in CRC tissues and cell lines. The effects of CPNE3 on proliferation, colony formation, migration, invasion, apoptosis, and autophagy were tested with gain- and loss-of-function experiments. Co-immunoprecipitation (IP), immunofluorescence, and Biological General Repository for Interaction Datasets (BIOGRID) analysis were used to find interacting proteins and pathways. KIF4 knockdown was performed to confirm functional rescue.

CPNE3 was upregulated in CRC. Silencing it reduced proliferation, migration, and invasion, and increased apoptosis and autophagy. Overexpression had opposite effects, increased KIF4 levels, activated PI3K/AKT/mTOR signaling, and suppressed autophagy markers (ATG5, ATG7, P62, LC3-II). CPNE3 directly interacted with KIF4. Knocking down KIF4 reversed the oncogenic effects of CPNE3 overexpression.

CPNE3 promotes CRC progression by interacting with KIF4 and regulating PI3K/AKT/mTOR and autophagy pathways. The CPNE3-KIF4 axis is a potential therapeutic target.