Therapeutic Delivery of MicroRNA-29b by Cationic Lipoplexes for Lung Cancer
MicroRNA-29b (miR-29b) expression has been shown to be reduced in non-small–cell lung cancer (NSCLC) tissues. Here, we have identified the oncogene cyclin-dependent protein kinase 6 (CDK6) as a direct target of miR-29b in lung cancer. We hypothesized that in vivo restoration of miR-29b and thus targ...
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doaj-6b9f9ac9debf40c292212de43cecb6ba2020-11-24T21:10:38ZengElsevierMolecular Therapy: Nucleic Acids2162-25312013-01-012C10.1038/mtna.2013.14Therapeutic Delivery of MicroRNA-29b by Cationic Lipoplexes for Lung CancerYun Wu0Melissa Crawford1Yicheng Mao2Robert J Lee3Ian C Davis4Terry S Elton5L James Lee6Serge P Nana-Sinkam7Center for Affordable Nanoengineering of Polymeric Biomedical Devices, 1012 Smith Lab, The Ohio State University, Columbus, Ohio, USADivision of Pulmonary, Allergy, Critical Care, and Sleep Medicine, College of Medicine, 201 Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USACenter for Affordable Nanoengineering of Polymeric Biomedical Devices, 1012 Smith Lab, The Ohio State University, Columbus, Ohio, USADivision of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, Ohio, USADepartment of Veterinary Sciences Biosciences, The Ohio State University, Columbus, Ohio, USAInternal Medicine, College of Medicine, 515 Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USACenter for Affordable Nanoengineering of Polymeric Biomedical Devices, 1012 Smith Lab, The Ohio State University, Columbus, Ohio, USADivision of Pulmonary, Allergy, Critical Care, and Sleep Medicine, College of Medicine, 201 Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USAMicroRNA-29b (miR-29b) expression has been shown to be reduced in non-small–cell lung cancer (NSCLC) tissues. Here, we have identified the oncogene cyclin-dependent protein kinase 6 (CDK6) as a direct target of miR-29b in lung cancer. We hypothesized that in vivo restoration of miR-29b and thus targeting of genes important to tumor initiation and progression may represent an option for lung cancer treatment. We developed a cationic lipoplexes (LPs)-based carrier that efficiently delivered miR-29b both in vitro and in vivo. LPs containing miR-29b (LP-miR-29b) efficiently delivered miR-29b to NSCLC A549 cells, reduced the expression of key targets CDK6, DNMT3B, and myeloid cell leukemia sequence 1 (MCL1), as well as cell growth and clonogenicity of A549 cells. In addition, the IC50 for cisplatin in the miR-29b–treated cells was effectively reduced. In a xenograft murine model, LPs efficiently accumulated at tumor sites. Systemic delivery of LP-miR-29b increased the tumor miR-29b expression by approximately fivefold, downregulated the tumor mRNA expression of CDK6, DNMT3B, and MCL1 by ~57.4, ~40.5, and ~52.4%, respectively, and significantly inhibited tumor growth by ~60% compared with LP-miR-NC (negative control). Our results demonstrate that cationic LPs represent an efficient delivery system that holds great potential in the development of miRNA-based therapeutics for lung cancer treatment.http://www.sciencedirect.com/science/article/pii/S2162253116301457cationic lipoplexeslung cancermicroRNA |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yun Wu Melissa Crawford Yicheng Mao Robert J Lee Ian C Davis Terry S Elton L James Lee Serge P Nana-Sinkam |
spellingShingle |
Yun Wu Melissa Crawford Yicheng Mao Robert J Lee Ian C Davis Terry S Elton L James Lee Serge P Nana-Sinkam Therapeutic Delivery of MicroRNA-29b by Cationic Lipoplexes for Lung Cancer Molecular Therapy: Nucleic Acids cationic lipoplexes lung cancer microRNA |
author_facet |
Yun Wu Melissa Crawford Yicheng Mao Robert J Lee Ian C Davis Terry S Elton L James Lee Serge P Nana-Sinkam |
author_sort |
Yun Wu |
title |
Therapeutic Delivery of MicroRNA-29b by Cationic Lipoplexes for Lung Cancer |
title_short |
Therapeutic Delivery of MicroRNA-29b by Cationic Lipoplexes for Lung Cancer |
title_full |
Therapeutic Delivery of MicroRNA-29b by Cationic Lipoplexes for Lung Cancer |
title_fullStr |
Therapeutic Delivery of MicroRNA-29b by Cationic Lipoplexes for Lung Cancer |
title_full_unstemmed |
Therapeutic Delivery of MicroRNA-29b by Cationic Lipoplexes for Lung Cancer |
title_sort |
therapeutic delivery of microrna-29b by cationic lipoplexes for lung cancer |
publisher |
Elsevier |
series |
Molecular Therapy: Nucleic Acids |
issn |
2162-2531 |
publishDate |
2013-01-01 |
description |
MicroRNA-29b (miR-29b) expression has been shown to be reduced in non-small–cell lung cancer (NSCLC) tissues. Here, we have identified the oncogene cyclin-dependent protein kinase 6 (CDK6) as a direct target of miR-29b in lung cancer. We hypothesized that in vivo restoration of miR-29b and thus targeting of genes important to tumor initiation and progression may represent an option for lung cancer treatment. We developed a cationic lipoplexes (LPs)-based carrier that efficiently delivered miR-29b both in vitro and in vivo. LPs containing miR-29b (LP-miR-29b) efficiently delivered miR-29b to NSCLC A549 cells, reduced the expression of key targets CDK6, DNMT3B, and myeloid cell leukemia sequence 1 (MCL1), as well as cell growth and clonogenicity of A549 cells. In addition, the IC50 for cisplatin in the miR-29b–treated cells was effectively reduced. In a xenograft murine model, LPs efficiently accumulated at tumor sites. Systemic delivery of LP-miR-29b increased the tumor miR-29b expression by approximately fivefold, downregulated the tumor mRNA expression of CDK6, DNMT3B, and MCL1 by ~57.4, ~40.5, and ~52.4%, respectively, and significantly inhibited tumor growth by ~60% compared with LP-miR-NC (negative control). Our results demonstrate that cationic LPs represent an efficient delivery system that holds great potential in the development of miRNA-based therapeutics for lung cancer treatment. |
topic |
cationic lipoplexes lung cancer microRNA |
url |
http://www.sciencedirect.com/science/article/pii/S2162253116301457 |
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