<i>Lnc-C/EBPβ</i> Negatively Regulates the Suppressive Function of Myeloid-Derived Suppressor Cells

Gao, Yuan; Sun, Wei; Shang, Wencong; Li, Yuanyuan; Zhang, Dan; Wang, Tianze; Zhang, Xipeng; Zhang, Shiwu; Zhang, Yuan; Yang, Rongcun

doi:10.1158/2326-6066.cir-18-0108

Cited by 60 publications

(61 citation statements)

References 33 publications

(41 reference statements)

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“…The C/EBPβ transcription factor is highly expressed in immune cells compared to other liver cells such as hepatocytes. C/EBPβ is involved in myeloid cell function where it promotes tumor-induced tolerance and immune suppression (25)(26)(27). These data are in agreement with the specificity of rs975484-PRMT1 regulation to tumor associated macrophages but not hepatoma cells.…”

Section: Discussionsupporting

confidence: 83%

The polymorphism rs975484 in the protein arginine methyltransferase 1 gene modulates expression of immune checkpoint genes in hepatocellular carcinoma

Schonfeld

Zhao

Komatz

et al. 2020

Journal of Biological Chemistry

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Protein arginine methyltransferase 1 (PRMT1) is a key regulator of hepatic immune responses. Recently, we reported that PRMT1 regulates the tumor immune response in hepatocellular carcinoma (HCC). Here we found that PRMT1 expression in human HCC correlates with that of programmed cell death 1 ligand 1 (PD-L1), PD-L2, and other checkpoint genes. PRMT1 deletion in mice reduced PD-L1 and PD-L2 expression in tumors and reduced the efficiency of PD-1 antibody treatment in a diethylnitrosamine-induced HCC mouse model, suggesting that PRMT1 regulates the hepatic immune checkpoint. Mice had reduced PD-L1 and PD-L2 expression when PRMT1 was specifically deleted in tumor cells or macrophages, but PRMT1 deletion in dendritic cells did not alter PD-L1 and PD-L2 expression. rs975484 is a common polymorphism in the human PRMT1 gene promoter, and we found that it alters PRMT1 expression in blood monocytes and tumor-associated macrophages in human HCC. PRMT1 expression was higher in individuals with a GG genotype than in individuals with a CC genotype, and heterozygous carriers had intermediate expression. Luciferase reporter assays indicated that this differential expression is due to an extra C/EBPβ-binding site in the PRMT1 promoter of individuals carrying the minor G allele. The rs975484 genotype also correlated with PRMT1 target expression in HCC. Individuals with the GG genotype had significantly higher levels of the PRMT1 targets PD-L1, PD-L2, and VISTA than those with the CC genotype. We conclude that PRMT1 critically controls immune checkpoints in mice and humans and that the PRMT1 polymorphism rs975484 affects checkpoint gene expression in HCC.

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Section: Discussionsupporting

confidence: 83%

The polymorphism rs975484 in the protein arginine methyltransferase 1 gene modulates expression of immune checkpoint genes in hepatocellular carcinoma

Schonfeld

Zhao

Komatz

et al. 2020

Journal of Biological Chemistry

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“…The C/EBPβ was overexpressed according to the development of granulocytic differentiation ( 151 , 152 ). LncRNA called lnc-C/EBPβ was described by Gao et al ( 132 ) They confirmed that lnc-C/EBPβ controls numerous transcripts in MDSCs to regulate MDSC differentiation and suppressive activity in inflammatory and tumor milieus. Expression of lnc-C/EBPβ via MDSCs, negatively controls MDSC function, signifying that lnc-C/EBPβ has a negative feedback function in avoiding over-suppression of MDSCs on immune reactions ( 132 ).…”

Section: Long Non-coding Rnasmentioning

confidence: 80%

“…LncRNA called lnc-C/EBPβ was described by Gao et al ( 132 ) They confirmed that lnc-C/EBPβ controls numerous transcripts in MDSCs to regulate MDSC differentiation and suppressive activity in inflammatory and tumor milieus. Expression of lnc-C/EBPβ via MDSCs, negatively controls MDSC function, signifying that lnc-C/EBPβ has a negative feedback function in avoiding over-suppression of MDSCs on immune reactions ( 132 ). Moreover, it is revealed that lnc-C/EBPβ can increase polymorphonuclear MDSCs (PMN-MDSC) but inhibit the differentiation of monocytic MDSCs (Mo-MDSC).…”

Section: Long Non-coding Rnasmentioning

confidence: 80%

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MicroRNAs and lncRNAs—A New Layer of Myeloid-Derived Suppressor Cells Regulation

et al. 2020

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Myeloid-derived suppressor cells (MDSCs) constitute an important component in regulating immune responses in several abnormal physiological conditions such as cancer. Recently, novel regulatory tumor MDSC biology modulating mechanisms, including differentiation, expansion and function, were defined. There is growing evidence that miRNAs and long non-coding RNAs (lncRNA) are involved in modulating transcriptional factors to become complex regulatory networks that regulate the MDSCs in the tumor microenvironment. It is possible that aberrant expression of miRNAs and lncRNA contributes to MDSC biological characteristics under pathophysiological conditions. This review provides an overview on miRNAs and lncRNAs epiregulation of MDSCs development and immunosuppressive functions in cancer.

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“…They are able to control function and differentiation of MDSCs in the TIME by regulating the downstream genes, C/EBPβ isoform LIP or/and CHOP (Fig. 5 ) [ 52 , 54 , 55 ]. Lnc-C/EBPβ binds the C/EBPβ isoform LIP to inhibit activation of C/EBPβ, affecting expansion of a suite of target transcripts including Arg-1, COX2, NOS2, NOX2 [ 52 , 126 ].…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA: a dazzling dancer in tumor immune microenvironment

Zhang

Liu

Liao

2020

J Exp Clin Cancer Res

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Long noncoding RNAs (lncRNAs) are a class of endogenous, non-protein coding RNAs that are highly linked to various cellular functions and pathological process. Emerging evidence indicates that lncRNAs participate in crosstalk between tumor and stroma, and reprogramming of tumor immune microenvironment (TIME). TIME possesses distinct populations of myeloid cells and lymphocytes to influence the immune escape of cancer, the response to immunotherapy, and the survival of patients. However, hitherto, a comprehensive review aiming at relationship between lncRNAs and TIME is missing. In this review, we focus on the functional roles and molecular mechanisms of lncRNAs within the TIME. Furthermore, we discussed the potential immunotherapeutic strategies based on lncRNAs and their limitations.

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Lnc-C/EBPβ Negatively Regulates the Suppressive Function of Myeloid-Derived Suppressor Cells

Cited by 60 publications

References 33 publications

The polymorphism rs975484 in the protein arginine methyltransferase 1 gene modulates expression of immune checkpoint genes in hepatocellular carcinoma

The polymorphism rs975484 in the protein arginine methyltransferase 1 gene modulates expression of immune checkpoint genes in hepatocellular carcinoma

MicroRNAs and lncRNAs—A New Layer of Myeloid-Derived Suppressor Cells Regulation

Long noncoding RNA: a dazzling dancer in tumor immune microenvironment

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