MUC1 promotes the proliferation and invasion of lung cancer cells by regulating PI3K/AKT pathway

Mucin 1 (MUC1) has been found to be significantly up-regulated in various types of cancer. However, the precise role and underlying mechanisms of MUC1 in lung cancer remain elusive. In this study, MUC1 expression was markedly elevated in lung cancer tissues and cell lines. Patients with low MUC1 expression showed improved overall survival rates compared to those with high expression levels. Additionally, knockdown of MUC1 significantly inhibited the viability and proliferation of A549 and H1299 cells, as demonstrated by CCK-8, EdU and colony formation assays. Flow cytometry analysis revealed that down-regulation of MUC1 induced apoptosis, decreased the protein expression levels of Bcl-2, and increased the expressions of Bax, caspase-3 and caspase-9 in both cell lines. Additionally, wound healing, Transwell migration and invasion assays indicated that down-regulation of MUC1 suppressed the migration and invasion capacities of A549 and H1299 cells, while also reducing the expression levels of MMP-2, MMP-9 and COX-2. Moreover, sh-MUC1 inhibited the epithelial-mesenchymal transition (EMT) progress in both cell lines. Interestingly, low MUC1 expression was associated with reduced activation of the PI3K/AKT signaling pathway. As expected, over-expression of MUC1 exerted the opposite effects. Furthermore, the PI3K/AKT inhibitor LY294002 enhanced the effects of sh-MUC1 on the proliferation, apoptosis, migration, invasion and EMT progress, while the activator SC79 partially restored these effects. Finally, down-regulation of MUC1 inhibited the tumorigenesis in nude mice by modulating the PI3K/AKT signaling pathway. To conclude, these findings suggested that MUC1 played an important role in lung cancer progression, potentially through the PI3K/AKT pathway. This positioned MUC1 as a molecule worthy of further investigation for its therapeutic potential.