期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 89, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.intimp.2020.107071
关键词
Hepatocellular carcinoma; LncRNA; MIAT; Immune; Sorafenib
资金
- Scientific and Technological Innovation Joint Capital Projects of Fujian Province [2017Y9100]
- National Natural Science Foundation of China [81470872]
- Natural Science Foundation of Fujian Province [2018J01296]
- Medical Innovation Project of Fujian Province [2017-CX-19]
- Startup Fund for scientific research of Fujian Medical University [2019QH2020]
- Construction Project of the Fujian Province Minimally Invasive Medical Center [[2017]171]
Long non-coding RNA (lncRNA) is a kind of important molecules involved in the formation of immune landscape in tumor microenvironment. However, there are few studies on the relationship between lncRNA and immunomodulatory regulation of hepatocellular carcinoma (HCC). In this study, we combined with single cell transcriptome sequencing and TCGA data to analyze the relationship between lncRNA MIAT and immune cells in HCC. TIMER database analysis indicated that the expression of MIAT in HCC was negatively correlated with tumor purity, positively correlated with the number of immune cells such as B cells, T lymphocytes and macrophages, and positively correlated with the expression of immune checkpoint molecules such as PD-1, PD-L1 and CTLA4. Analysis of single cell sequencing data of immune cells in HCC showed that MIAT was mainly distributed in tumor, and enriched in FOXP3(+)CD4(+)T cells and PDCD1(+)CD8(+), GZMK(+)CD8(+)T cells, indicating that MIAT may be involved in the immune escape process of HCC. Besides, through the construction of transcription factor (TF) regulatory network, MIAT-TF-mRNA, we found that the interaction of MIAT and TFs may affect the immune microenvironment of LIHC by regulating the expression of target genes JAK2, SLC6A6, KCND1, MEIS3 or RIN1; LncMAP and CARE analysis showed that MIAT was highly related to the sensitivity of many anticancer drugs, especially sorafenib. In addition, the effect of MIAT on PD-L1 and its relationship with sorafinib were verified in clinical specimens and cells. This study made a meaningful attempt to reveal the immune escape mechanism and to find the effectiveness of targeted drugs in patients with HCC.
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