18F-FDG PET/CT for Monitoring the Response of Breast Cancer to miR-143-Based Therapeutics by Targeting Tumor Glycolysis
Increased glucose utilization is a hallmark of cancer, and tumor metabolism is emerging as anticancer target for therapeutic intervention. Triple-negative breast cancers TNBC are highly glycolytic and show poor clinical outcomes. We previously identified hexokinase 2, the major glycolytic enzyme, as...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-01-01
|
| Series: | Molecular Therapy: Nucleic Acids |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S216225311730080X |
| _version_ | 1819209319095205888 |
|---|---|
| author | Ying Miao Ling-fei Zhang Rui Guo Sheng Liang Min Zhang Shuo Shi Cheng-fang Shang-Guan Mo-fang Liu Biao Li |
| author_facet | Ying Miao Ling-fei Zhang Rui Guo Sheng Liang Min Zhang Shuo Shi Cheng-fang Shang-Guan Mo-fang Liu Biao Li |
| author_sort | Ying Miao |
| collection | DOAJ |
| description | Increased glucose utilization is a hallmark of cancer, and tumor metabolism is emerging as anticancer target for therapeutic intervention. Triple-negative breast cancers TNBC are highly glycolytic and show poor clinical outcomes. We previously identified hexokinase 2, the major glycolytic enzyme, as a target gene of miR-143 in TNBC. Here, we developed a therapeutic formulation using cholesterol-modified miR-143 agomir encapsulated in a neutral lipid-based delivery agent that blocked tumor growth and glucose metabolism in TNBC tumor-bearing mice when administered systemically. The antioncogenic effects were accompanied by a reduction in the direct target hexokinase 2 and [18F]-fluorodeoxyglucose (18F-FDG) uptake based on positron emission tomography/computed tomography. Treatment with miR-143 formulation has minimal toxic effects and mice tolerated it well. Thus, we demonstrated that miR-143 is a robust inhibitor of the Warburg effect and an effective therapeutic target for TNBC. In addition, 18F-FDG positron emission tomography/computed tomography can be used to specifically monitor the response of TNBC to miR-143-based therapeutics by targeting tumor glycolysis. |
| first_indexed | 2024-12-23T05:53:23Z |
| format | Article |
| id | doaj.art-b221e66d73b946cda4498e7e7163d3bf |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-23T05:53:23Z |
| publishDate | 2016-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-b221e66d73b946cda4498e7e7163d3bf2022-12-21T17:57:53ZengElsevierMolecular Therapy: Nucleic Acids2162-25312016-01-015C10.1038/mtna.2016.7218F-FDG PET/CT for Monitoring the Response of Breast Cancer to miR-143-Based Therapeutics by Targeting Tumor GlycolysisYing Miao0Ling-fei Zhang1Rui Guo2Sheng Liang3Min Zhang4Shuo Shi5Cheng-fang Shang-Guan6Mo-fang Liu7Biao Li8Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaCenter for RNA Research, State Key Laboratory of Molecular Biology-University of Chinese Academy of Sciences, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, ChinaDepartment of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Nuclear Medicine, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaCenter for RNA Research, State Key Laboratory of Molecular Biology-University of Chinese Academy of Sciences, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, ChinaDepartment of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaIncreased glucose utilization is a hallmark of cancer, and tumor metabolism is emerging as anticancer target for therapeutic intervention. Triple-negative breast cancers TNBC are highly glycolytic and show poor clinical outcomes. We previously identified hexokinase 2, the major glycolytic enzyme, as a target gene of miR-143 in TNBC. Here, we developed a therapeutic formulation using cholesterol-modified miR-143 agomir encapsulated in a neutral lipid-based delivery agent that blocked tumor growth and glucose metabolism in TNBC tumor-bearing mice when administered systemically. The antioncogenic effects were accompanied by a reduction in the direct target hexokinase 2 and [18F]-fluorodeoxyglucose (18F-FDG) uptake based on positron emission tomography/computed tomography. Treatment with miR-143 formulation has minimal toxic effects and mice tolerated it well. Thus, we demonstrated that miR-143 is a robust inhibitor of the Warburg effect and an effective therapeutic target for TNBC. In addition, 18F-FDG positron emission tomography/computed tomography can be used to specifically monitor the response of TNBC to miR-143-based therapeutics by targeting tumor glycolysis.http://www.sciencedirect.com/science/article/pii/S216225311730080X |
| spellingShingle | Ying Miao Ling-fei Zhang Rui Guo Sheng Liang Min Zhang Shuo Shi Cheng-fang Shang-Guan Mo-fang Liu Biao Li 18F-FDG PET/CT for Monitoring the Response of Breast Cancer to miR-143-Based Therapeutics by Targeting Tumor Glycolysis Molecular Therapy: Nucleic Acids |
| title | 18F-FDG PET/CT for Monitoring the Response of Breast Cancer to miR-143-Based Therapeutics by Targeting Tumor Glycolysis |
| title_full | 18F-FDG PET/CT for Monitoring the Response of Breast Cancer to miR-143-Based Therapeutics by Targeting Tumor Glycolysis |
| title_fullStr | 18F-FDG PET/CT for Monitoring the Response of Breast Cancer to miR-143-Based Therapeutics by Targeting Tumor Glycolysis |
| title_full_unstemmed | 18F-FDG PET/CT for Monitoring the Response of Breast Cancer to miR-143-Based Therapeutics by Targeting Tumor Glycolysis |
| title_short | 18F-FDG PET/CT for Monitoring the Response of Breast Cancer to miR-143-Based Therapeutics by Targeting Tumor Glycolysis |
| title_sort | 18f fdg pet ct for monitoring the response of breast cancer to mir 143 based therapeutics by targeting tumor glycolysis |
| url | http://www.sciencedirect.com/science/article/pii/S216225311730080X |
| work_keys_str_mv | AT yingmiao 18ffdgpetctformonitoringtheresponseofbreastcancertomir143basedtherapeuticsbytargetingtumorglycolysis AT lingfeizhang 18ffdgpetctformonitoringtheresponseofbreastcancertomir143basedtherapeuticsbytargetingtumorglycolysis AT ruiguo 18ffdgpetctformonitoringtheresponseofbreastcancertomir143basedtherapeuticsbytargetingtumorglycolysis AT shengliang 18ffdgpetctformonitoringtheresponseofbreastcancertomir143basedtherapeuticsbytargetingtumorglycolysis AT minzhang 18ffdgpetctformonitoringtheresponseofbreastcancertomir143basedtherapeuticsbytargetingtumorglycolysis AT shuoshi 18ffdgpetctformonitoringtheresponseofbreastcancertomir143basedtherapeuticsbytargetingtumorglycolysis AT chengfangshangguan 18ffdgpetctformonitoringtheresponseofbreastcancertomir143basedtherapeuticsbytargetingtumorglycolysis AT mofangliu 18ffdgpetctformonitoringtheresponseofbreastcancertomir143basedtherapeuticsbytargetingtumorglycolysis AT biaoli 18ffdgpetctformonitoringtheresponseofbreastcancertomir143basedtherapeuticsbytargetingtumorglycolysis |