A combinatorial microRNA therapeutics approach to suppressing non-small cell lung cancer.
Andrea L. Kasinski,Kevin Kelnar,Carlos Stahlhut,Esteban A. Orellana,Jane Zhao,Eliot Shimer,Sarah Dysart,Xiaowei Chen,Andreas G. Bader,Frank J. Slack +9 more
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TLDR
This combinatorial miRNA therapeutic approach engages numerous components of tumor cell-addictive pathways and highlights the ability to deliver multiple miRNAs in a safe and effective manner to target lung tissue.Abstract:
Targeted cancer therapies, although often effective, have limited utility owing to preexisting primary or acquired secondary resistance. Consequently, agents are sometimes used in combination to simultaneously affect multiple targets. MicroRNA mimics are excellent therapeutic candidates because of their ability to repress multiple oncogenic pathways at once. Here we treated the aggressive Kras;p53 non-small cell lung cancer mouse model and demonstrated efficacy with a combination of two tumor-suppressive microRNAs (miRNAs). Systemic nanodelivery of miR-34 and let-7 suppressed tumor growth leading to survival advantage. This combinatorial miRNA therapeutic approach engages numerous components of tumor cell-addictive pathways and highlights the ability to deliver multiple miRNAs in a safe and effective manner to target lung tissue.read more
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Journal Article
The let-7 microrna reduces tumor growth in mouse models of lung cancer
Aurora Esquela-Kerscher,Phong Trang,Lance Ford,David Brown,Joanne B. Weidhaas,Frank J. Slack +5 more
TL;DR: Findings provide direct evidence that let-7 acts as a tumor suppressor gene in the lung and indicate that this miRNA may be useful as a novel therapeutic agent in lung cancer.
Journal ArticleDOI
A network-biology perspective of microRNA function and dysfunction in cancer
Cameron P. Bracken,Cameron P. Bracken,Hamish S. Scott,Hamish S. Scott,Gregory J. Goodall,Gregory J. Goodall +5 more
TL;DR: Advances in experimental and computational approaches are revealing not just cancer pathways controlled by single miRNAAs but also intermeshed regulatory networks controlled by multiple miRNAs, which often engage in reciprocal feedback interactions with the targets that they regulate.
Journal ArticleDOI
Targeting noncoding RNAs in disease
TL;DR: The continued improvement of innovative RNA modifications and delivery entities, such as nanoparticles, will aid in the development of future RNA-based therapeutics for a broader range of chronic diseases.
Journal ArticleDOI
Pathophysiology of cardiac hypertrophy and heart failure: signaling pathways and novel therapeutic targets.
Yow Keat Tham,Yow Keat Tham,Bianca C. Bernardo,Jenny Y. Y. Ooi,Kate L. Weeks,Julie R. McMullen,Julie R. McMullen +6 more
TL;DR: New therapeutic approaches either entering clinical trials or in preclinical development, and the challenges that remain in translating these discoveries to new and approved therapies for heart failure are addressed.
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MicroRNA-34 family: a potential tumor suppressor and therapeutic candidate in cancer.
Lu Zhang,Yi Liao,Liling Tang +2 more
TL;DR: In this article, the authors provide an overview about the function of microRNA-34 in various cancers and the mechanism of miR34 in tumor-associated EMT, and their potential role as a microRNA therapeutic candidate is also discussed.
References
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NIH Image to ImageJ: 25 years of image analysis
TL;DR: The origins, challenges and solutions of NIH Image and ImageJ software are discussed, and how their history can serve to advise and inform other software projects.
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The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans
Brenda J. Reinhart,Frank J. Slack,Frank J. Slack,Michael Basson,Amy E. Pasquinelli,Bettinger Jc,Ann E. Rougvie,H R Horvitz,Gary Ruvkun +8 more
TL;DR: It is shown that let-7 is a heterochronic switch gene that encodes a temporally regulated 21-nucleotide RNA that is complementary to elements in the 3′ untranslated regions of the heteroch chronic genes lin-14, lin-28, Lin-41, lin -42 and daf-12, indicating that expression of these genes may be directly controlled by let- 7.
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RAS Is Regulated by the let-7 MicroRNA Family
Steven M. Johnson,Helge Grosshans,Jaclyn Shingara,Mike Byrom,Rich Jarvis,Angie Cheng,Emmanuel Labourier,Kristy L. Reinert,David Brown,Frank J. Slack +9 more
TL;DR: It is shown that the let-7 family negatively regulates let-60/RAS, a regulatory RNAs found in multicellular eukaryotes, including humans, where they are implicated in cancer.
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Unique microRNA molecular profiles in lung cancer diagnosis and prognosis
Nozomu Yanaihara,Natasha J. Caplen,Elise D. Bowman,Masahiro Seike,Kensuke Kumamoto,Ming Yi,Robert M. Stephens,Aikou Okamoto,Jun Yokota,Tadao Tanaka,George A. Calin,Chang Gong Liu,Carlo M. Croce,Curtis C. Harris +13 more
TL;DR: Results indicate that miRNA expression profiles are diagnostic and prognostic markers of lung cancer.
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A microRNA component of the p53 tumour suppressor network
Lin He,Xingyue He,Xingyue He,Lee P. Lim,Elisa de Stanchina,Elisa de Stanchina,Zhenyu Xuan,Yu Liang,Wen Xue,Lars Zender,Jill F. Magnus,Dana Ridzon,Aimee L. Jackson,Peter S. Linsley,Caifu Chen,Scott W. Lowe,Michele A. Cleary,Gregory J. Hannon +17 more
TL;DR: A family of miRNAs, miR-34a–c, whose expression reflected p53 status is described, whose encoded genes are direct transcriptional targets of p53, whose induction by DNA damage and oncogenic stress depends on p53 both in vitro and in vivo.