CHMP4C promotes the progression and cisplatin resistance of non-small cell lung cancer via the PI3K/AKT signaling pathway

Abstract

Abstract Aims The objective of this study was to investigate the expression and mechanism of chromatin-modifying protein 4C (CHMP4C) in non-small cell lung cancer (NSCLC). The study aimed to provide novel perspectives on the diagnosis and treatment of NSCLC. Methods In order to investigate the impact of CHMP4C on NSCLC, the expression of CHMP4C and its correlation with the prognosis of patients were examined by the GEPIA platform and UALCAN database. To validate the expression, immunohistochemistry (IHC), quantitative real-time PCR (qPCR), and western blot experiments were conducted. Additionally, lentivirus (shRNA) technology was utilized to downregulate the expression of in H1299 and SKMES1 cells. Cell Counting Kit-8 (CCK-8) and cell clone assays were performed to assess cell proliferation and the role of CHMP4C in regulating cisplatin sensitivity. The cell cycle and apoptosis were detected using Flow Cytometry. Furthermore, the relationship between CHMP4C and the PI3K/AKT signaling pathway was investigated through western blotting. Results CHMP4C exhibited a high level of expression in both NSCLC tissues and cell lines. Additionally, the expression of CHMP4C was significantly associated with the TNM stage of the tumors, and higher CHMP4C expression was linked to poorer prognosis. The results of the cell experiments showed that CHMP4C expression was significantly higher in H1299 and SKMES1 cells compared to the normal lung epithelial cells BEAS-2B. Suppression of CHMP4C significantly impeded the proliferation of H1299 and SKMES1 cells by delaying the cell cycle and promoting apoptosis through the PI3K/AKT signaling pathway. Moreover, an interesting phenomenon was made during the study: the expression of CHMP4C protein was reduced by cisplatin treatment. Knockdown of CHMP4C enhanced the therapeutic sensitivity of NSCLC cells to cisplatin. Conclusion CHMP4C plays a crucial role in NSCLC proliferation and cisplatin resistance, potentially through the PI3K/AKT signaling pathway. These findings provide valuable experimental evidence for the clinical treatment of NSCLC.