Circ_0000052/miR‐382‐3p axis induces PD‐L1 expression and regulates cell proliferation and immune evasion in head and neck squamous cell carcinoma

A better understanding of the mechanisms underlying PD‐L1 aberrant expression in head and neck squamous cell carcinoma (HNSCC) will help reveal predictive biomarkers and overcome resistance to treatment. In this study, the prognostic significance of PD‐L1 in forty‐five HNSCC archival samples was determined by qRT‐PCR. The biological function associated with malignant behaviour was assessed by PD‐L1 depletion, miR‐382‐3p re‐expression and regulation of circ_0000052. The interactions of PD‐L1‐miRNA and miRNA‐circRNA were determined by qRT‐PCR, Western blot analysis, dual‐luciferase reporter assays and RNA immunoprecipitation assays. PD‐L1 was highly expressed in patient samples and cancer cell lines. Higher levels of PD‐L1 were associated with patient recurrences and play a pivotal role in regulating cell proliferation, migration, invasion, clonogenicity and apoptosis. In addition to demonstrating that the IFN‐γ/JAK2/STAT1 signalling pathway can induce PD‐L1 overexpression in HNSCC, a novel mechanism by which upregulated circ_0000052 mediates PD‐L1 overexpression was also demonstrated. To do this, circ_0000052 competitively binds to miR‐382‐3p and alleviates its repression of PD‐L1. This leads to overexpression of PD‐L1, causing the aggressiveness of the cells. Our data demonstrate that circ_0000052 is oncogenic, and the circ_0000052/miR‐382‐3p/PD‐L1 axis is critical in HNSCC progression. The manipulation of circRNAs/miRNAs in combination with anti‐PD‐L1 therapy may improve personalized disease management.