A novel IFN?-induced long noncoding RNA negatively regulates immunosuppression by interrupting H3K27 acetylation in head and neck squamous cell carcinoma.

ABSTRACT: BACKGROUND:Interferon alpha (IFN?) is a well-established regulator of immunosuppression in head and neck squamous cell carcinoma (HNSCC), while the role of long noncoding RNAs (lncRNAs) in immunosuppression remains largely unknown. METHODS:Differentially expressed lncRNAs were screened under IFN? stimulation using lncRNA sequencing. The role and mechanism of lncRNA in immunosuppression were investigated in HNSCC in vitro and in vivo. RESULTS:We identified a novel IFN?-induced upregulated lncRNA, lncMX1-215, in HNSCC. LncMX1-215 was primarily located in the cell nucleus. Ectopic expression of lncMX1-215 markedly inhibited expression of the IFN?-induced, immunosuppression-related molecules programmed cell death 1 ligand 1 (PD-L1) and galectin-9, and vice versa. Subsequently, histone deacetylase (HDAC) inhibitors promoted the expression of PD-L1 and galectin-9. Binding sites for H3K27 acetylation were found on PD-L1 and galectin-9 promoters. Mechanistically, we found that lncMX1-215 directly interacted with GCN5, a known H3K27 acetylase, to interrupt its binding to H3K27 acetylation. Clinically, negative correlations between lncMX1-215 and PD-L1 and galectin-9 expression were observed. Finally, overexpression of lncMX1-215 suppressed HNSCC proliferation and metastasis capacity in vitro and in vivo. CONCLUSIONS:Our results suggest that lncMX1-215 negatively regulates immunosuppression by interrupting GCN5/H3K27ac binding in HNSCC, thus providing novel insights into immune checkpoint blockade treatment.

SUBMITTER: Ma H 

PROVIDER: S-EPMC6943933 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature