EpCAM-Targeted 3WJ RNA Nanoparticle Harboring Delta-5-Desaturase siRNA Inhibited Lung Tumor Formation via DGLA Peroxidation
Knocking down delta-5-desaturase (D5D) expression by D5D small interfering RNA (siRNA) has been reported that could redirect the cyclooxygenase-2 (COX-2)-catalyzed dihomo-γ-linolenic acid (DGLA) peroxidation from producing prostaglandin E2 to 8-hydroxyoctanoic acid (8-HOA), resulting in the inhibiti...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-12-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253120302535 |
| _version_ | 1818724363307843584 |
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| author | Lizhi Pang Harshit Shah Hongzhi Wang Dan Shu Steven Y. Qian Venkatachalem Sathish |
| author_facet | Lizhi Pang Harshit Shah Hongzhi Wang Dan Shu Steven Y. Qian Venkatachalem Sathish |
| author_sort | Lizhi Pang |
| collection | DOAJ |
| description | Knocking down delta-5-desaturase (D5D) expression by D5D small interfering RNA (siRNA) has been reported that could redirect the cyclooxygenase-2 (COX-2)-catalyzed dihomo-γ-linolenic acid (DGLA) peroxidation from producing prostaglandin E2 to 8-hydroxyoctanoic acid (8-HOA), resulting in the inhibition of colon and pancreatic cancers. However, the effect of D5D siRNA on lung cancer is still unknown. In this study, by incorporating epithelial cell adhesion molecule (EpCAM) aptamer and validated D5D siRNA into the innovative three-way junction (3WJ) RNA nanoparticle, target-specific accumulation and D5D knockdown were achieved in the lung cancer cell and mouse models. By promoting the 8-HOA formation from the COX-2-catalyzed DGLA peroxidation, the 3WJ-EpCAM-D5D siRNA nanoparticle inhibited lung cancer growth in vivo and in vitro. As a potential histone deacetylases inhibitor, 8-HOA subsequently inhibited cancer proliferation and induced apoptosis via suppressing YAP1/TAZ nuclear translocation and expression. Therefore, this 3WJ-RNA nanoparticle could improve the targeting and effectiveness of D5D siRNA in lung cancer therapy. |
| first_indexed | 2024-12-17T21:25:13Z |
| format | Article |
| id | doaj.art-a6e26193aa3640e99d722ec2e98e7807 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-17T21:25:13Z |
| publishDate | 2020-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-a6e26193aa3640e99d722ec2e98e78072022-12-21T21:32:03ZengElsevierMolecular Therapy: Nucleic Acids2162-25312020-12-0122222235EpCAM-Targeted 3WJ RNA Nanoparticle Harboring Delta-5-Desaturase siRNA Inhibited Lung Tumor Formation via DGLA PeroxidationLizhi Pang0Harshit Shah1Hongzhi Wang2Dan Shu3Steven Y. Qian4Venkatachalem Sathish5Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58102, USADepartment of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58102, USACenter for RNA Nanobiotechnology and Nanomedicine, The Ohio State University, Columbus, OH 43210, USA; College of Pharmacy, Division of Pharmaceutics and Pharmaceutical Chemistry, The Ohio State University, Columbus, OH 43210, USA; College of Medicine, Dorothy M. Davis Heart and Lung Research Institute and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USACenter for RNA Nanobiotechnology and Nanomedicine, The Ohio State University, Columbus, OH 43210, USA; College of Pharmacy, Division of Pharmaceutics and Pharmaceutical Chemistry, The Ohio State University, Columbus, OH 43210, USA; College of Medicine, Dorothy M. Davis Heart and Lung Research Institute and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USADepartment of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58102, USADepartment of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58102, USA; Corresponding author: Venkatachalem Sathish, Department of Pharmaceutical Sciences, North Dakota State University, Sudro 203, 1401 Albrecht Blvd., Fargo, ND 58102, USA.Knocking down delta-5-desaturase (D5D) expression by D5D small interfering RNA (siRNA) has been reported that could redirect the cyclooxygenase-2 (COX-2)-catalyzed dihomo-γ-linolenic acid (DGLA) peroxidation from producing prostaglandin E2 to 8-hydroxyoctanoic acid (8-HOA), resulting in the inhibition of colon and pancreatic cancers. However, the effect of D5D siRNA on lung cancer is still unknown. In this study, by incorporating epithelial cell adhesion molecule (EpCAM) aptamer and validated D5D siRNA into the innovative three-way junction (3WJ) RNA nanoparticle, target-specific accumulation and D5D knockdown were achieved in the lung cancer cell and mouse models. By promoting the 8-HOA formation from the COX-2-catalyzed DGLA peroxidation, the 3WJ-EpCAM-D5D siRNA nanoparticle inhibited lung cancer growth in vivo and in vitro. As a potential histone deacetylases inhibitor, 8-HOA subsequently inhibited cancer proliferation and induced apoptosis via suppressing YAP1/TAZ nuclear translocation and expression. Therefore, this 3WJ-RNA nanoparticle could improve the targeting and effectiveness of D5D siRNA in lung cancer therapy.http://www.sciencedirect.com/science/article/pii/S21622531203025353WJ RNA nanoparticleDGLA peroxidationHDACnon-small cell lung cancerYAP1/TAZ pathway |
| spellingShingle | Lizhi Pang Harshit Shah Hongzhi Wang Dan Shu Steven Y. Qian Venkatachalem Sathish EpCAM-Targeted 3WJ RNA Nanoparticle Harboring Delta-5-Desaturase siRNA Inhibited Lung Tumor Formation via DGLA Peroxidation Molecular Therapy: Nucleic Acids 3WJ RNA nanoparticle DGLA peroxidation HDAC non-small cell lung cancer YAP1/TAZ pathway |
| title | EpCAM-Targeted 3WJ RNA Nanoparticle Harboring Delta-5-Desaturase siRNA Inhibited Lung Tumor Formation via DGLA Peroxidation |
| title_full | EpCAM-Targeted 3WJ RNA Nanoparticle Harboring Delta-5-Desaturase siRNA Inhibited Lung Tumor Formation via DGLA Peroxidation |
| title_fullStr | EpCAM-Targeted 3WJ RNA Nanoparticle Harboring Delta-5-Desaturase siRNA Inhibited Lung Tumor Formation via DGLA Peroxidation |
| title_full_unstemmed | EpCAM-Targeted 3WJ RNA Nanoparticle Harboring Delta-5-Desaturase siRNA Inhibited Lung Tumor Formation via DGLA Peroxidation |
| title_short | EpCAM-Targeted 3WJ RNA Nanoparticle Harboring Delta-5-Desaturase siRNA Inhibited Lung Tumor Formation via DGLA Peroxidation |
| title_sort | epcam targeted 3wj rna nanoparticle harboring delta 5 desaturase sirna inhibited lung tumor formation via dgla peroxidation |
| topic | 3WJ RNA nanoparticle DGLA peroxidation HDAC non-small cell lung cancer YAP1/TAZ pathway |
| url | http://www.sciencedirect.com/science/article/pii/S2162253120302535 |
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