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A combinatorial microRNA therapeutics approach to suppressing non-small cell lung cancer.

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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.

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Journal Article

The let-7 microrna reduces tumor growth in mouse models of lung cancer

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.
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A network-biology perspective of microRNA function and dysfunction in cancer

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.
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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.
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Pathophysiology of cardiac hypertrophy and heart failure: signaling pathways and novel therapeutic targets.

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.
Journal ArticleDOI

MicroRNA-34 family: a potential tumor suppressor and therapeutic candidate in cancer.

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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Journal ArticleDOI

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

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

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.
Journal ArticleDOI

A microRNA component of the p53 tumour suppressor network

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.
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