Targeting USP22 with miR­30­5p to inhibit the hypoxia­induced expression of PD­L1 in lung adenocarcinoma cells.

Lung cancer is one of the most common forms of cancer and accounts for a significant proportion of all cancer­related deaths. Lung adenocarcinoma (LUAD) accounts for approximately 40% of all cases of lung cancer. In recent years, new developments in both the diagnosis and treatment of LUAD have been achieved. Unfortunately, the prognosis remains poor for patients with malignant LUAD. Hypoxia is a common characteristic of solid tumors and induce the immune evasion by increasing the expression of programmed cell death­ligand­1 (PD­L1) in the tumor. In this study, it was predicted that ubiquitin­specific peptidase 22 (USP22) is the direct target of the microRNA (miR)­30­5p family, including miR­30a­5p, miR­30b­5p, miR­30c­5p, miR­30d­5p and miR­30e­5p. Furthermore, the binding of USP22 with the miR­30­5p family was confirmed by luciferase assay. In addition, it was demonstrated that targeting USP22 via the miR­30­5p family inhibited the induction of PD­L1 expression in hypoxic conditions, thus preventing activated T cells from killing LUAD cells. Our results indicated that miR­30a­5p, miR­30b­5p, miR­30c­5p, miR­30d­5p and miR­30e­5p represent new targets for the treatment of LUAD.