Pluto Bioinformatics

GSE138147: A novel IFN-induced long noncoding RNA, lncMX1-215, negatively regulates immunosuppression by interrupting H3K27 acetylation in head and neck squamous cell carcinoma

Bulk RNA sequencing

Interferon-alpha (IFN) plays a ciritical role in immune regulation, especially in tumor microenvironment. Our previous study has demonstrated that IFN promoted immunosuppression formation in head and neck squamous cell carcinoma. To explore the mechanism underlying IFN-induced immunosuppression, long noncoding RNA (lncRNA) sequece was conduted. We identified a novel IFN-induced upregulated lncRNA, lncMX1-215 in HNSCC. It was mainly located in cell nucleus. Ectopic expression of lncMX1-215 markedly inhibited IFN-induced immunosuppression molecules, programmed cell death 1 ligand 1(PD-L1) and galectin-9 expression, and vice versa. Subsequently, histone deacetylase (HDAC) inhibitors promoted the expression of PD-L1 and galectin-9. There were binding sites of H3K27 acetylation on PD-L1 and galectin-9 promoters. Mechanically, we find 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, galectin-9 were observed. Finally, overexpression of lncMX1-215 suppressed the proliferation and metastasis capacity in vitro and in vivo in HNSCC. Our results suggest that lncMX1-215 negatively regulates immunosuppression through interrupting GCN5/H3K27ac in HNSCC and provides novel insights into immune checkpoint blockade treatment. SOURCE: Hailong Ma (mahl21@sjtu.edu.cn) - Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine