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         headline:PD-L1 lncRNA splice isoform promotes lung adenocarcinoma progression via enhancing c-Myc activity
         description:Although using a blockade of programmed death-ligand 1 (PD-L1) to enhance T cell immune responses shows great promise in tumor immunotherapy, the immune-checkpoint inhibition strategy is limited for patients with solid tumors. The mechanism and efficacy of such immune-checkpoint inhibition strategies in solid tumors remains unclear. Employing qRT-PCR, Sanger sequencing, and RNA BaseScope analysis, we show that human lung adenocarcinoma (LUAD) all produce a long non-coding RNA isoform of PD-L1 (PD-L1-lnc) by alternative splicing, regardless if the tumor is positive or negative for the protein PD-L1. Similar to PD-L1 mRNA, PD-L1-lnc in various lung adenocarcinoma cells is significantly upregulated by IFNγ. Both in vitro and in vivo studies demonstrate that PD-L1-lnc increases proliferation and invasion but decreases apoptosis of lung adenocarcinoma cells. Mechanistically, PD-L1-lnc promotes lung adenocarcinoma progression through directly binding to c-Myc and enhancing c-Myc transcriptional activity. In summary, the PD-L1 gene can generate a long non-coding RNA through alternative splicing to promote lung adenocarcinoma progression by enhancing c-Myc activity. Our results argue in favor of investigating PD-L1-lnc depletion in combination with PD-L1 blockade in lung cancer therapy.
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      headline:PD-L1 lncRNA splice isoform promotes lung adenocarcinoma progression via enhancing c-Myc activity
      description:Although using a blockade of programmed death-ligand 1 (PD-L1) to enhance T cell immune responses shows great promise in tumor immunotherapy, the immune-checkpoint inhibition strategy is limited for patients with solid tumors. The mechanism and efficacy of such immune-checkpoint inhibition strategies in solid tumors remains unclear. Employing qRT-PCR, Sanger sequencing, and RNA BaseScope analysis, we show that human lung adenocarcinoma (LUAD) all produce a long non-coding RNA isoform of PD-L1 (PD-L1-lnc) by alternative splicing, regardless if the tumor is positive or negative for the protein PD-L1. Similar to PD-L1 mRNA, PD-L1-lnc in various lung adenocarcinoma cells is significantly upregulated by IFNγ. Both in vitro and in vivo studies demonstrate that PD-L1-lnc increases proliferation and invasion but decreases apoptosis of lung adenocarcinoma cells. Mechanistically, PD-L1-lnc promotes lung adenocarcinoma progression through directly binding to c-Myc and enhancing c-Myc transcriptional activity. In summary, the PD-L1 gene can generate a long non-coding RNA through alternative splicing to promote lung adenocarcinoma progression by enhancing c-Myc activity. Our results argue in favor of investigating PD-L1-lnc depletion in combination with PD-L1 blockade in lung cancer therapy.
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      dateModified:2021-04-13T00:00:00Z
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         Plant Genetics and Genomics
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         Bioinformatics
         Evolutionary Biology
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         type:PostalAddress
      name:China Pharmaceutical University
      address:
         name:School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
         type:PostalAddress
      name:Nanjing University
      address:
         name:State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, China
         type:PostalAddress
ImageObject:
      url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
Person:
      name:Shuang Qu
      affiliation:
            name:Nanjing University
            address:
               name:State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, China
               type:PostalAddress
            type:Organization
            name:China Pharmaceutical University
            address:
               name:School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Zichen Jiao
      affiliation:
            name:Department of Thoracic Surgery, Nanjing Drum Tower Hospital, Medical School, Nanjing University
            address:
               name:Department of Thoracic Surgery, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Geng Lu
      affiliation:
            name:Nanjing University
            address:
               name:Department of Emergency Medicine, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Bing Yao
      affiliation:
            name:Nanjing Medical University
            address:
               name:Department of Medical Genetics, Nanjing Medical University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Ting Wang
      affiliation:
            name:Nanjing University
            address:
               name:Department of Pathology, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Weiwei Rong
      affiliation:
            name:Nanjing University
            address:
               name:State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Jiahan Xu
      affiliation:
            name:Nanjing University
            address:
               name:Department of General Surgery, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Ting Fan
      affiliation:
            name:Nanjing University
            address:
               name:Department of Gastroenterology, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Xinlei Sun
      affiliation:
            name:Nanjing University
            address:
               name:State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Rong Yang
      affiliation:
            name:Nanjing University
            address:
               name:State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Jun Wang
      affiliation:
            name:Nanjing University
            address:
               name:Department of Emergency Medicine, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Yongzhong Yao
      affiliation:
            name:Nanjing University
            address:
               name:Department of General Surgery, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Guifang Xu
      affiliation:
            name:Nanjing University
            address:
               name:Department of Gastroenterology, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Xin Yan
      affiliation:
            name:Nanjing University
            address:
               name:Department of Respiratory Medicine, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Tao Wang
      affiliation:
            name:Department of Thoracic Surgery, Nanjing Drum Tower Hospital, Medical School, Nanjing University
            address:
               name:Department of Thoracic Surgery, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Hongwei Liang
      affiliation:
            name:Nanjing University
            address:
               name:State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, China
               type:PostalAddress
            type:Organization
            name:China Pharmaceutical University
            address:
               name:School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Ke Zen
      affiliation:
            name:Nanjing University
            address:
               name:State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, China
      name:School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
      name:Department of Thoracic Surgery, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China
      name:Department of Emergency Medicine, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China
      name:Department of Medical Genetics, Nanjing Medical University, Nanjing, China
      name:Department of Pathology, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China
      name:State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, China
      name:Department of General Surgery, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China
      name:Department of Gastroenterology, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China
      name:State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, China
      name:State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, China
      name:Department of Emergency Medicine, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China
      name:Department of General Surgery, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China
      name:Department of Gastroenterology, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China
      name:Department of Respiratory Medicine, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China
      name:Department of Thoracic Surgery, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China
      name:State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, China
      name:School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
      name:State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, China

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