SQSTM1/P62 Mediates the Effects of CPNE3 on the Epithelialmesenchymal Transition and Migratory Inhibition of Lung Adenocarcinoma Cells.

Abstract

Introduction: Copine-3 (CPNE3) is a conservative calcium-dependent phospholipid-binding protein belonging to the copines protein family. CPNE3 has been implicated in the development and progression of several diseases, including cancer.

Method: Herein, we investigated the molecular mechanisms through which CPNE3 regulates the migration of lung adenocarcinoma (LUAD) cells in vitro. Western blotting and immunohistochemical assays showed that CPNE3 is widely distributed in LUAD tissues and cell lines and that CPNE3 downregulation promotes the migration of human LUAD A549 cells.

Results: Stable isotope labelling with amino acids in cell culture, which is a quantitative proteomics approach coupled with bioinformatic analyses, revealed that CPNE3 regulates SQSTM1/p62 and vimentin expression, indicating that CPNE3 may mediate epithelial-mesenchymal transition (EMT). CPNE3 silencing by siRNA upregulated vimentin levels but downregulated E-cadherin levels in the A549 cells.

Conclusion: Furthermore, SQSTM1/p62 knockdown enhanced migratory ability and EMT progression in CPNE3-silenced A549 cells. Overall, CPNE3 knockdown was found to promote EMT by inhibiting SQSTM1/p62 signalling and facilitating cell migration. Our findings highlight the role of CPNE3 as a tumour suppressor, providing deeper insights into its carcinogenic roles in LUAD.