RNA Nanoparticle-Based Targeted Therapy for Glioblastoma through Inhibition of Oncogenic miR-21

Lee, Tae Jin; Yoo, Ji Young; Shu, Dan; Li, Hui; Zhang, Jianying; Yu, Jun; Jaime-Ramirez, Alena Cristina; Acunzo, Mario; Romano, Giulia; Cui, Ri; Sun, Hui; Luo, Zhenghua; Old, Matthew; Kaur, Balveen; Guo, Peixuan; Croce, Carlo M.

doi:10.1016/j.ymthe.2016.11.016

Cited by 120 publications

(88 citation statements)

References 43 publications

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“…Similar results have been previously observed using anti-miR-10b in mammary tumors 26 and anti-miR-21 in glioblastomas. 27 Interestingly, in our breast tumor models miR-214 levels diminished in primary tumors, while miR-148b expression increased. As a consequence, miR-148b direct targets, ALCAM and ITGA5, were found reduced.…”

Section: Discussionmentioning

confidence: 68%

Therapeutic Silencing of miR-214 Inhibits Tumor Progression in Multiple Mouse Models

et al. 2018

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We previously demonstrated that miR-214 is upregulated in malignant melanomas and triple-negative breast tumors and promotes metastatic dissemination by affecting a complex pathway including the anti-metastatic miR-148b. Importantly, tumor dissemination could be reduced by blocking miR-214 function or increasing miR-148b expression or by simultaneous interventions. Based on this evidence, with the intent to explore the role of miR-214 as a target for therapy, we evaluated the capability of new chemically modified anti-miR-214, R97/R98, to inhibit miR-214 coordinated metastatic traits. Relevantly, when melanoma or breast cancer cells were transfected with R97/R98, anti-miR-214 reduced miR-214 expression and impaired transendothelial migration were observed. Noteworthy, when the same cells were injected in the tail vein of mice, cell extravasation and metastatic nodule formation in lungs were strongly reduced. Thus, suggesting that R97/R98 anti-miR-214 oligonucleotides were able to inhibit tumor cell escaping through the endothelium. More importantly, when R97/R98 anti-miR-214 compounds were systemically delivered to mice carrying melanomas or breast or neuroendocrine pancreatic cancers, a reduced number of circulating tumor cells and lung or lymph node metastasis formation were detected. Similar results were also obtained when AAV8-miR-214 sponges were used in neuroendocrine pancreatic tumors. Based on this evidence, we propose miR-214 as a promising target for anti-metastatic therapies.

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Section: Discussionmentioning

confidence: 68%

Therapeutic Silencing of miR-214 Inhibits Tumor Progression in Multiple Mouse Models

et al. 2018

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“…Expression of miR‐21 is elevated in human glioma cells, and LNA against miR‐21 can efficiently inhibit tumor growth in a xenograft‐model of human glioblastoma . MRG‐106, an inhibitor of miR‐155, has been studied in phase I clinical trials (http://www.miragen.com).…”

Section: Therapeutic Approaches Based On Mirna Regulationmentioning

confidence: 99%

Development of miRNA‐based therapeutic approaches for cancer patients

Takahashi

Prieto‐Vila

Kohama³

et al. 2019

Cancer Science

109

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Over the past few decades, si RNA and mi RNA have attracted a great deal of attention from researchers and clinicians. These molecules have been extensively studied from the standpoint of developing biopharmaceuticals against various diseases, including heart disease, diabetes and cancers. si RNA suppresses only a single target, whereas each mi RNA regulates the expression of multiple target genes. More importantly, because mi RNA are also secreted from cancer cells, and their aberrant expression is associated with tumor development and progression, they represent not only therapeutic targets but also promising biomarkers for diagnosis and prognosis. Therefore, mi RNA may be more effective tools against cancers, in which multiple signal pathways are dysregulated. In this review, we summarize recent progress in the development of mi RNA therapeutics for the treatment of cancer patients, and describe delivery systems for oligonucleotide therapeutics.

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“…Despite numerous studies which support the functionality of eRNAs, the relevance and implications are currently debated and there is no final consensus as to the mechanisms of eRNA regulation and function. One challenging part is that eRNAs are expressed at low levels and unstable, and most of them are expressed only in the nucleus, which make approaches to degrade eRNAs via RNA interference (RNAi) not suitable [144][145][146]. Using a polyadenylation signal to terminate eRNA expression will perhaps provide an alternative way to interfere with eRNA function [147,148].…”

Section: Role Of Enhancer-transcribed Ernasmentioning

confidence: 99%

Loss of the co-repressor GPS2 sensitizes macrophage activation upon metabolic stress induced by obesity and type 2 diabetes

Fan

Toubal

Goñi

et al. 2016

Nat Med

135

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Humans with obesity differ in their susceptibility to developing insulin resistance and type 2 diabetes (T2D). This variation may relate to the extent of adipose tissue (AT) inflammation that develops as their obesity progresses. The state of macrophage activation has a central role in determining the degree of AT inflammation and thus its dysfunction, and these states are driven by epigenomic alterations linked to gene expression. The underlying mechanisms that regulate these alterations, however, are poorly defined. Here we demonstrate that a co-repressor complex containing G protein pathway suppressor 2 (GPS2) crucially controls the macrophage epigenome during activation by metabolic stress. The study of AT from humans with and without obesity revealed correlations between reduced GPS2 expression in macrophages, elevated systemic and AT inflammation, and diabetic status. The causality of this relationship was confirmed by using macrophage-specific Gps2-knockout (KO) mice, in which inappropriate co-repressor complex function caused enhancer activation, pro-inflammatory gene expression and hypersensitivity toward metabolic-stress signals. By contrast, transplantation of GPS2-overexpressing bone marrow into two mouse models of obesity (ob/ob and diet-induced obesity) reduced inflammation and improved insulin sensitivity. Thus, our data reveal a potentially reversible disease mechanism that links co-repressor-dependent epigenomic alterations in macrophages to AT inflammation and the development of T2D.

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RNA Nanoparticle-Based Targeted Therapy for Glioblastoma through Inhibition of Oncogenic miR-21

Cited by 120 publications

References 43 publications

Therapeutic Silencing of miR-214 Inhibits Tumor Progression in Multiple Mouse Models

Therapeutic Silencing of miR-214 Inhibits Tumor Progression in Multiple Mouse Models

Development of miRNA‐based therapeutic approaches for cancer patients

Loss of the co-repressor GPS2 sensitizes macrophage activation upon metabolic stress induced by obesity and type 2 diabetes

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