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Topics {✒️}

shmir-30a/e-5p sirna-mir-30b-5p hep1–6-shmir-30a/e-5p cells biotin-labeled mir-30-5p mimics mir-30-5p/snail/ dpp4/cxcl10 axis circmet/mir-30-5p/snail/dpp4 axis hepg2-shmir-30a/e-5p hepg2-simir-30d-5p cells compared contributed reagents/materials/analysis tools shmir-30a/e-5p cells mir-30a/e-5p knockdown mir-30-5p/snail/dpp4 axis wt-mir-30a-5p compared hcclm3-mir-30a-5p compared shmir-30a/e-5p cd26/dpp4 inhibitor vildagliptin sirna-mir-30d-5p sirna-mir-30c-5p dpp4-promoter-luc-oe vectors mir-30a/e-5p tumor-specific t-cell response circmet/snail/ dpp4/cxcl10 axis mitogen-activated protein kinase mu-mir-30s-5p si-mir-30b-5p guo-ming shi si-mir-30d-5p mutant-mir-30a-5p si-mir-30c-5p full-length wild type sh/si-mir-30-5p wt-mir-30s-5p virus-related hepatocellular carcinoma hepg2-simir-30b-5p ai-wu ke dual-luciferase assays showed mouse mutant-mir-30-5p mir-30a-5p expression hepg2-simir-30c-5p article download pdf hep-1-6-shmir-30s cells mir-30-5p binding sites snail/dpp4/cxcl10 axis snail/ dpp4/cxcl10 axis liquid protein chip anti-pd1 therapy resistance specific pathogen-free conditions high/low metastatic capacity anti-pd1 antibody therapy dual-luciferase reporter assay anti-pd1 antibodies combined

Schema {🗺️}

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         headline:Circular RNA circMET drives immunosuppression and anti-PD1 therapy resistance in hepatocellular carcinoma via the miR-30-5p/snail/DPP4 axis
         description:Amplification of chromosome 7q21-7q31 is associated with tumor recurrence and multidrug resistance, and several genes in this region are powerful drivers of hepatocellular carcinoma (HCC). We aimed to investigate the key circular RNAs (circRNAs) in this region that regulate the initiation and development of HCC. We used qRT-PCR to assess the expression of 43 putative circRNAs in this chromosomal region in human HCC and matched nontumor tissues. In addition, we used cultured HCC cells to modify circRNA expression and assessed the effects in several cell-based assays as well as gene expression analyses via RNA-seq. Modified cells were implanted into immunocompetent mice to assess the effects on tumor development. We performed additional experiments to determine the mechanism of action of these effects. circMET (hsa_circ_0082002) was overexpressed in HCC tumors, and circMET expression was associated with survival and recurrence in HCC patients. By modifying the expression of circMET in HCC cells in vitro, we found that circMET overexpression promoted HCC development by inducing an epithelial to mesenchymal transition and enhancing the immunosuppressive tumor microenvironment. Mechanistically, circMET induced this microenvironment through the miR-30-5p/Snail/ dipeptidyl peptidase 4(DPP4)/CXCL10 axis. In addition, the combination of the DPP4 inhibitor sitagliptin and anti-PD1 antibody improved antitumor immunity in immunocompetent mice. Clinically, HCC tissues from diabetic patients receiving sitagliptin showed higher CD8+ T cell infiltration than those from HCC patients with diabetes without sitagliptin treatment. circMET is an onco-circRNA that induces HCC development and immune tolerance via the Snail/DPP4/CXCL10 axis. Furthermore, sitagliptin may enhance the efficacy of anti-PD1 therapy in a subgroup of patients with HCC.
         datePublished:2020-05-19T00:00:00Z
         dateModified:2024-02-29T00:00:00Z
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            Hepatocellular carcinogenesis
            circRNA
            miR-30-5p
            circMET
            DPP4
            Cancer Research
            Oncology
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                     address:
                        name:Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, P.R. China
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      headline:Circular RNA circMET drives immunosuppression and anti-PD1 therapy resistance in hepatocellular carcinoma via the miR-30-5p/snail/DPP4 axis
      description:Amplification of chromosome 7q21-7q31 is associated with tumor recurrence and multidrug resistance, and several genes in this region are powerful drivers of hepatocellular carcinoma (HCC). We aimed to investigate the key circular RNAs (circRNAs) in this region that regulate the initiation and development of HCC. We used qRT-PCR to assess the expression of 43 putative circRNAs in this chromosomal region in human HCC and matched nontumor tissues. In addition, we used cultured HCC cells to modify circRNA expression and assessed the effects in several cell-based assays as well as gene expression analyses via RNA-seq. Modified cells were implanted into immunocompetent mice to assess the effects on tumor development. We performed additional experiments to determine the mechanism of action of these effects. circMET (hsa_circ_0082002) was overexpressed in HCC tumors, and circMET expression was associated with survival and recurrence in HCC patients. By modifying the expression of circMET in HCC cells in vitro, we found that circMET overexpression promoted HCC development by inducing an epithelial to mesenchymal transition and enhancing the immunosuppressive tumor microenvironment. Mechanistically, circMET induced this microenvironment through the miR-30-5p/Snail/ dipeptidyl peptidase 4(DPP4)/CXCL10 axis. In addition, the combination of the DPP4 inhibitor sitagliptin and anti-PD1 antibody improved antitumor immunity in immunocompetent mice. Clinically, HCC tissues from diabetic patients receiving sitagliptin showed higher CD8+ T cell infiltration than those from HCC patients with diabetes without sitagliptin treatment. circMET is an onco-circRNA that induces HCC development and immune tolerance via the Snail/DPP4/CXCL10 axis. Furthermore, sitagliptin may enhance the efficacy of anti-PD1 therapy in a subgroup of patients with HCC.
      datePublished:2020-05-19T00:00:00Z
      dateModified:2024-02-29T00:00:00Z
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      pageEnd:18
      license:http://creativecommons.org/publicdomain/zero/1.0/
      sameAs:https://doi.org/10.1186/s12943-020-01213-6
      keywords:
         Hepatocellular carcinogenesis
         circRNA
         miR-30-5p
         circMET
         DPP4
         Cancer Research
         Oncology
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            name:Xiao-Yong Huang
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                  name:Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University
                  address:
                     name:Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, P.R. China
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                     name:Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, P.R. China
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            address:
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            address:
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            address:
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               type:PostalAddress
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      name:Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, P.R. China
      name:Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, P.R. China
      name:Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, P.R. China
      name:Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, P.R. China
      name:Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, P.R. China
      name:Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, P.R. China
      name:Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, P.R. China
      name:Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, P.R. China
      name:Cancer Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, P.R. China
      name:Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, P.R. China
      name:Cancer Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, P.R. China
      name:Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, P.R. China
      name:Cancer Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, P.R. China
      name:State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China
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      name:Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, P.R. China
      name:Cancer Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, P.R. China

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