Funding
National Natural Science Foundation of China
Harbin Medical University Cancer Hospital
Heilongjiang Provincial Natural Science Foundation
Wu Lien-teh Science Foundation
Harbin Medical University
Distinguished Young Scholars
Yong Elite Training Foundation
Haiyan Fund
ARTICLE ABSTRACT
Long noncoding RNAs (lncRNA) that are associated with immune checkpoints have not been identified, and the mechanism by which such lncRNAs might regulate the expression of immune checkpoints is unknown in human cancer. Immune checkpoint–associated lncRNAs (ICP-lncRNA) were identified and validated via a comprehensive bioinformatic analysis of The Cancer Genome Atlas data. These ICP-lncRNAs were involved in key immune response and immune cell receptor signaling pathways. The expression of ICP-lncRNAs was upregulated and correlated with a poor prognosis in patients with cancer. HLA complex P5 (HCP5) and myocardial infarction associated transcript (MIAT) promoted tumor growth and upregulated the expression of PD-L1/CD274 via a competing endogenous RNA mechanism of sponging miR-150-5p. The combination of MIAT knockdown and PD-L1 antibody administration showed a synergistic inhibitory effect on tumor growth. Finally, the expression of both HCP5 and MIAT was confirmed to be transcriptionally suppressed by CCCTC-binding factor (CTCF), and lipopolysaccharide induced CTCF eviction from the HCP5 and MIAT promoters, attenuating the transcriptionally suppressive activity of CTCF. This study enlarges the functional landscape of known lncRNAs in human cancer and indicates novel insights into their roles in the field of tumor immunity and immunotherapy. These findings may aid in the comprehensive management of human cancer with immunotherapy.
