NEDD4L suppresses PD-L1 expression and enhances anti-tumor immune response in A549 cells

Non-small cell lung cancer (NSCLC) poses a salient threat to public health. E3 ubiquitin ligase commonly functions as an anti-tumor role.This study probed the effect of E3 ligase NEDD4L on A549 cells.NEDD4L expression in NSCLC and its correlation with NSCLC patient's prognosis were predicted and verified. PD-L1 protein level was measured, and the correlation between NEDD4L and PD-L1 was analyzed. The effects of NEDD4L overexpression on the binding of NEDD4L to PD-L1 and ubiquitination level of PD-L1 were examined. Xenograft tumor model was established in mice. The volume and weight of xenograft tumors were recorded. The proportion of CD8NEDD4L expression was downregulated in NSCLC tissues and A549 cells, and correlated with poor prognosis of NSCLC patients. PD-L1 was upregulated in NSCLC and negatively correlated with NEDD4L. Overexpression of NEDD4L upregulated ubiquitination level of PD-L1 and reduced protein level of PD-L1. Overexpression of NEDD4L decreased tumor volume and weight and enhanced proportion of CD8Collectively, overexpression of NEDD4L suppressed PD-L1 protein level through ubiquitination, thereby enhancing anti-tumor immune response and retarding NSCLC progression.