NEXN targeting MYOCD by facilitating EMT-related β-catenin nuclear translocation modulates the metastasis of hepatocellular carcinoma.

Nexilin F-actin binding protein (NEXN) is crucial for myocardial structural integrity, but its role in HCC progression is unclear. This study aimed to elucidate the role of NEXN in HCC. NEXN was weakly expressed in HCC, and its reduction correlated with poorer overall, disease-free, and progression-free survival. Overexpressing NEXN inhibited cell proliferation, colony formation, migration, and invasion in vitro, as well as tumor formation in vivo. NEXN overexpression downregulated the expression of mesenchymal markers and partially upregulated E-cadherin expression. Mechanistically, NEXN overexpression reduced β-catenin nuclear accumulation. Furthermore, by binding to MYOCD, NEXN co-regulated the EMT in HCC through the WNT/β-catenin signaling pathway. In conclusion, the diminished expression of NEXN interacts with MYOCD, influencing poor HCC prognosis by promoting EMT via the NEXN-MYOCD-β-catenin signaling axis. These findings provide a preclinical foundation for the development of metastasis-targeting inhibitors within the WNT pathway.