HOTAIR Up-Regulation Activates NF-κB to Induce Immunoescape in Gliomas

作者：Yunfei Wang, Kaikai Yi, Xing Liu, Yanli Tan, Weili Jin, Yansheng Li, Junhu Zhou, Hongjun Wang, Chunsheng Kang · 发表于：Frontiers in Immunology · 年份：2021 · DOI：10.3389/fimmu.2021.785463 · 被引用次数：38 · 研究领域：Cancer-related molecular mechanisms research、Cancer Mechanisms and Therapy、interferon and immune responses

Background Checkpoint blockade therapies targeting programmed death ligand 1 (PD-L1) and its receptor programmed cell death 1 promote T cell-mediated immune surveillance against tumors and have been associated with significant clinical benefit in cancer patients. The long-stranded non-coding RNA HOTAIR is highly expressed and associated with metastasis in a variety of cancer types and promotes tumor metastasis at least in part through association with the PRC2 complex that induces redirection to hundreds of genes involved in tumor metastasis. Here, we report that HOTAIR is an activator lncRNA of the NF-κB pathway and demonstrate that its apparent upregulation promotes inflammatory signaling and immune escape in glioma cells. Methods Bioinformatics analysis was used to elucidate the relationship between HOTAIR and NF-κB pathway in HOTAIR knockdown glioma cells. At the cytological level, protein hybridization and immunofluorescence were used to detect the response of proteins in the NF-κB signaling pathway to HOTAIR regulation. ChIP and ChIRP experiments identified HOTAIR target genes. Animal experiments verified alterations in inflammation and immune escape following HOTAIR knockdown and activity inhibition. Results HOTAIR activated the expression of proteins involved in NF-κB, TNFα, MAPK and other inflammatory signaling pathways. In addition, HOTAIR induced various proteins containing protein kinase structural domains and promoted the enrichment of proteins and complexes of i...