Lipopolysaccharide facilitates immune escape of hepatocellular carcinoma cells via m6A modification of lncRNA MIR155HG to upregulate PD-L1 expression View Full Text


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Article Info

DATE

2022-04-19

AUTHORS

Lirong Peng, Banglun Pan, Xiaoxia Zhang, Zengbin Wang, Jiacheng Qiu, Xiaoqian Wang, Nanhong Tang

ABSTRACT

Recent studies have suggested that the initiation and progression of hepatocellular carcinoma (HCC) are closely associated with lipopolysaccharide (LPS) of intestinal bacteria. However, the role of LPS in immune regulation of HCC remains largely unknown. An orthotopic Hepa1-6 tumor model of HCC was constructed to analyze the effect of LPS on the expression of immune checkpoint molecules PD-1 and PD-L1. Then we verified the regulation of PD-L1 by LPS in HCC cells. Based on the previous finding that lncRNA MIR155HG regulates PD-L1 expression in HCC cells, we analyzed the relationship of LPS signaling pathway molecules with PD-L1 and MIR155HG by bioinformatics. The molecular mechanism of MIR155HG regulating PD-L1 expression induced by LPS was investigated by RNA pull-down followed by mass spectrometry, RNA immunoprecipitation, fluorescence in situ hybridization, and luciferase reporter assay. Finally, the HepG2 xenograft model was established to determine the role of MIR155HG on PD-L1 expression in vivo. We showed that LPS induced PD-1 and PD-L1 expression in mouse tumor tissues and induced PD-L1 expression in HCC cells. Mechanistically, upregulation of METTL14 by LPS promotes the m6A methylation of MIR155HG, which stabilizes MIR155HG relying on the “reader” protein ELAVL1 (also known as HuR)-dependent pathway. Moreover, MIR155HG functions as a competing endogenous RNA (ceRNA) to modulate the expression of PD-L1 by miR-223/STAT1 axis. Our results suggested that LPS plays a critical role in immune escape of HCC through METTL14/MIR155HG/PD-L1 axis. This study provides a new insight for understanding the complex immune microenvironment of HCC.Graphical abstract1. LPS plays a critical role in immune escape of HCC, especially HCC with cirrhosis.2. Our study reveals that LPS regulates PD-L1 by m6A modification of lncRNA in HCC.3. MIR155HG plays an important role in LPS induced PD-L1 expression.4. LPS-MIR155HG-PD-L1 regulatory axis provides a new target for the treatment of HCC. More... »

PAGES

1-15

References to SciGraph publications

  • 2017-06-22. LPS alters the immuno-phenotype of glioma and glioma stem-like cells and induces in vivo antitumor immunity via TLR4 in JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
  • 2007-10-21. TLR4 enhances TGF-β signaling and hepatic fibrosis in NATURE MEDICINE
  • 2017-10-09. Essential role of METTL3-mediated m6A modification in glioma stem-like cells maintenance and radioresistance in ONCOGENE
  • 2014-04-09. The dynamic epitranscriptome: N6-methyladenosine and gene expression control in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2020-09-05. LncRNA PSMB8-AS1 contributes to pancreatic cancer progression via modulating miR-382-3p/STAT1/PD-L1 axis in JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
  • 2019-05-02. Cellular functions of long noncoding RNAs in NATURE CELL BIOLOGY
  • 2017-11-23. An immune-related lncRNA signature for patients with anaplastic gliomas in JOURNAL OF NEURO-ONCOLOGY
  • 2018-01-29. The immunology of hepatocellular carcinoma in NATURE IMMUNOLOGY
  • 2019-05-07. Lipopolysaccharide induces the differentiation of hepatic progenitor cells into myofibroblasts constitutes the hepatocarcinogenesis-associated microenvironment in CELL DEATH & DIFFERENTIATION
  • 2009-11. STATs in cancer inflammation and immunity: a leading role for STAT3 in NATURE REVIEWS CANCER
  • 2019-06-27. A multipeptide vaccine plus toll-like receptor agonists LPS or polyICLC in combination with incomplete Freund’s adjuvant in melanoma patients in JOURNAL FOR IMMUNOTHERAPY OF CANCER
  • 2020-02-24. GNAS promotes inflammation-related hepatocellular carcinoma progression by promoting STAT3 activation in CELLULAR & MOLECULAR BIOLOGY LETTERS
  • 2016-11-03. Post-transcriptional gene regulation by mRNA modifications in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2018-09-17. NKILA lncRNA promotes tumor immune evasion by sensitizing T cells to activation-induced cell death in NATURE IMMUNOLOGY
  • 2019-06-03. Oncogenic lncRNA downregulates cancer cell antigen presentation and intrinsic tumor suppression in NATURE IMMUNOLOGY
  • 2019-10-16. Long noncoding RNA GAS5 inhibits progression of colorectal cancer by interacting with and triggering YAP phosphorylation and degradation and is negatively regulated by the m6A reader YTHDF3 in MOLECULAR CANCER
  • 2016-11-30. m6A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination in NATURE
  • 2018-07-21. Novel insights on m6A RNA methylation in tumorigenesis: a double-edged sword in MOLECULAR CANCER
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    24 schema:description Recent studies have suggested that the initiation and progression of hepatocellular carcinoma (HCC) are closely associated with lipopolysaccharide (LPS) of intestinal bacteria. However, the role of LPS in immune regulation of HCC remains largely unknown. An orthotopic Hepa1-6 tumor model of HCC was constructed to analyze the effect of LPS on the expression of immune checkpoint molecules PD-1 and PD-L1. Then we verified the regulation of PD-L1 by LPS in HCC cells. Based on the previous finding that lncRNA MIR155HG regulates PD-L1 expression in HCC cells, we analyzed the relationship of LPS signaling pathway molecules with PD-L1 and MIR155HG by bioinformatics. The molecular mechanism of MIR155HG regulating PD-L1 expression induced by LPS was investigated by RNA pull-down followed by mass spectrometry, RNA immunoprecipitation, fluorescence in situ hybridization, and luciferase reporter assay. Finally, the HepG2 xenograft model was established to determine the role of MIR155HG on PD-L1 expression in vivo. We showed that LPS induced PD-1 and PD-L1 expression in mouse tumor tissues and induced PD-L1 expression in HCC cells. Mechanistically, upregulation of METTL14 by LPS promotes the m6A methylation of MIR155HG, which stabilizes MIR155HG relying on the “reader” protein ELAVL1 (also known as HuR)-dependent pathway. Moreover, MIR155HG functions as a competing endogenous RNA (ceRNA) to modulate the expression of PD-L1 by miR-223/STAT1 axis. Our results suggested that LPS plays a critical role in immune escape of HCC through METTL14/MIR155HG/PD-L1 axis. This study provides a new insight for understanding the complex immune microenvironment of HCC.Graphical abstract1. LPS plays a critical role in immune escape of HCC, especially HCC with cirrhosis.2. Our study reveals that LPS regulates PD-L1 by m6A modification of lncRNA in HCC.3. MIR155HG plays an important role in LPS induced PD-L1 expression.4. LPS-MIR155HG-PD-L1 regulatory axis provides a new target for the treatment of HCC.
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    29 schema:keywords ELAVL1
    30 HCC cells
    31 HepG2 xenograft model
    32 METTL14
    33 MIR155HG
    34 Mechanistically
    35 PD-1
    36 PD-L1
    37 PD-L1 axis
    38 PD-L1 expression
    39 RNA
    40 RNA immunoprecipitation
    41 Recent studies
    42 axis
    43 bacteria
    44 bioinformatics
    45 carcinoma
    46 carcinoma cells
    47 cells
    48 checkpoint molecules PD-1
    49 cirrhosis
    50 complex immune microenvironment
    51 critical role
    52 dependent pathway
    53 effect
    54 effects of lipopolysaccharide
    55 endogenous RNA
    56 escape
    57 expression
    58 findings
    59 fluorescence
    60 function
    61 hepatocellular carcinoma
    62 hepatocellular carcinoma cells
    63 hybridization
    64 immune checkpoint molecules PD-1
    65 immune escape
    66 immune microenvironment
    67 immune regulation
    68 immunoprecipitation
    69 important role
    70 initiation
    71 insights
    72 intestinal bacteria
    73 lipopolysaccharide
    74 lncRNA MIR155HG
    75 lncRNAs
    76 luciferase reporter
    77 m6A methylation
    78 m6A modification
    79 mass spectrometry
    80 mechanism
    81 methylation
    82 microenvironment
    83 model
    84 modification
    85 molecular mechanisms
    86 molecules
    87 mouse tumor tissues
    88 new insights
    89 new targets
    90 pathway
    91 pathway molecules
    92 previous findings
    93 progression
    94 protein ELAVL1
    95 readers
    96 regulation
    97 regulatory axis
    98 relationship
    99 reporter
    100 results
    101 role
    102 role of lipopolysaccharide
    103 situ hybridization
    104 spectrometry
    105 study
    106 target
    107 tissue
    108 treatment
    109 treatment of HCC
    110 tumor model
    111 tumor tissue
    112 upregulation
    113 vivo
    114 xenograft model
    115 schema:name Lipopolysaccharide facilitates immune escape of hepatocellular carcinoma cells via m6A modification of lncRNA MIR155HG to upregulate PD-L1 expression
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