Long Noncoding RNAs Control the Modulation of Immune Checkpoint Molecules in Cancer
- 1 July 2020
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Cancer Immunology Research
- Vol. 8 (7), 937-951
- https://doi.org/10.1158/2326-6066.cir-19-0696
Abstract
Long noncoding RNAs (lncRNAs) 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 long noncoding RNAs (ICP-lncRNAs) were identified and validated via a comprehensive bioinformatic analysis of The Cancer Genome Atlas (TCGA) 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 cancer patients. 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 (ceRNA) 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 (LPS) 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 finding may aid in the comprehensive management of human cancer with immunotherapy.Keywords
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Funding Information
- National Natural Science Foundation of China (81972706, 81602323, 81872149)
- Harbin Medical University Cancer Hospital (Nn102017-02)
- Heilongjiang Provincial Natural Science Foundation (YQ2019H027)
- Wu Lien-teh Science Foundation Harbin Medical University (WLD-QN1706)
- Distinguished Young Scholars Harbin Medical University Cancer Hospital (JCQN2018-03)
- Yong Elite Training Foundation Harbin Medical University Cancer Hospital (JY2016-02)
- Haiyan Fund Harbin Medical University Cancer Hospital (JJQN 2018-10)
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