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1.
Oncotarget ; 10(57): 5892-5893, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31666921
2.
Cell Cycle ; 18(15): 1798-1811, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31258013

RESUMO

Efforts to search for better treatment options for cancer have been a priority, and due to these efforts, new alternative therapies have emerged. For instance, clinically relevant tumor-suppressive microRNAs that target key oncogenic drivers have been identified as potential anti-cancer therapeutics. MicroRNAs are small non-coding RNAs that negatively regulate gene expression at the posttranscriptional level. Aberrant microRNA expression, through misexpression of microRNA target genes, can have profound cellular effects leading to a variety of diseases, including cancer. While altered microRNA expression contributes to a cancerous state, restoration of microRNA expression has therapeutic benefits. For example, ectopic expression of microRNA-34a (miR-34a), a tumor suppressor gene that is a direct transcriptional target of p53 and thus is reduced in p53 mutant tumors, has clear effects on cell proliferation and survival in murine models of cancer. MicroRNA replacement therapies have recently been tested in combination with other agents, including other microRNAs, to simultaneously target multiple pathways to improve the therapeutic response. Thus, we reasoned that other microRNA combinations could collaborate to further improve treatment. To test this hypothesis miR-34a was used in an unbiased cell-based approach to identify combinatorial microRNA pairs with enhanced efficacy over miR-34a alone. This approach identified a subset of microRNAs that was able to enhance the miR-34a antiproliferative activity. These microRNA combinatorial therapeutics could offer superior tumor-suppressive abilities to suppress oncogenic properties compared to a monotherapeutic approach. Collectively these studies aim to address an unmet need of identifying, characterizing, and therapeutically targeting microRNAs for the treatment of cancer.

3.
Mol Ther Nucleic Acids ; 16: 505-518, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31071527

RESUMO

The therapeutic promise of small-RNA therapeutics is limited, not only by the lack of delivery vehicles, but also by the inability of the small RNAs to reach intracellular compartments where they can be biologically active. We previously reported successful delivery of functionally active miRNAs via receptor-mediated endocytosis. This type of targeted therapy still faces a major challenge in the delivery field: endosomal sequestration. Here, a new method has been developed to promote endosomal escape of delivered miRNA. The strategy relies on the difference in solute contents between nascent endosomes and the cytoplasm; early endosomes are rich in sodium ions, whereas the intracellular fluid is rich is potassium ions. Exploiting this difference through favoring the influx of potassium into the endosomes without the exchange of osmotically active sodium, results in an osmotic differential leading to the endosomes swelling and bursting. One molecule that is able to exchange potassium for an osmotically inactive hydrogen ion is the ionophore nigericin. Through generating an intramolecular miRNA delivery vehicle, containing a ligand, in this case folate and nigericin, we enabled the escape of folate-RNA conjugates from their entrapping endosomes into the cytoplasm where they bound the RNA-induced silencing complex and activated the RNAi response.

4.
Cell Rep ; 22(7): 1810-1823, 2018 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-29444433

RESUMO

MicroRNA-223 is known as a myeloid-enriched anti-inflammatory microRNA that is dysregulated in numerous inflammatory conditions. Here, we report that neutrophilic inflammation (wound response) is augmented in miR-223-deficient zebrafish, due primarily to elevated activation of the canonical nuclear factor κB (NF-κB) pathway. NF-κB over-activation is restricted to the basal layer of the surface epithelium, although miR-223 is detected throughout the epithelium and in phagocytes. Not only phagocytes but also epithelial cells are involved in miR-223-mediated regulation of neutrophils' wound response and NF-κB activation. Cul1a/b, Traf6, and Tab1 are identified as direct targets of miR-223, and their levels rise in injured epithelium lacking miR-223. In addition, miR-223 is expressed in cultured human bronchial epithelial cells, where it also downregulates NF-κB signaling. Together, this direct connection between miR-223 and the canonical NF-κB pathway provides a mechanistic understanding of the multifaceted role of miR-223 and highlights the relevance of epithelial cells in dampening neutrophil activation.


Assuntos
Inflamação/patologia , Queratinócitos/metabolismo , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Neutrófilos/patologia , Transdução de Sinais , Nadadeiras de Animais/fisiologia , Animais , Sequência de Bases , Brônquios/citologia , Embrião não Mamífero/metabolismo , Células Epiteliais/metabolismo , Células HEK293 , Humanos , Inflamação/metabolismo , MicroRNAs/genética , Neutrófilos/metabolismo , Fagócitos/metabolismo , Regeneração , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
5.
Bioconjug Chem ; 29(4): 1047-1059, 2018 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-29446616

RESUMO

Although peptides, antibodies/antibody fragments, siRNAs, antisense DNAs, enzymes, and aptamers are all under development as possible therapeutic agents, the breadth of their applications has been severely compromised by their inability to reach intracellular targets. Thus, while macromolecules can often enter cells by receptor-mediated endocytosis, their missions frequently fail due to an inability to escape their entrapping endosomes. In this paper, we describe a general method for promoting release of any biologic material from any entrapping endosome. The strategy relies on the fact that all nascent endosomes contain extracellular (Na+-enriched) medium, but are surrounded by intracellular (K+-enriched) fluid in the cytoplasm. Osmotic swelling and rupture of endosomes will therefore be facilitated if the flow of K+ down its concentration gradient from the cytosol into the endosome can be facilitated without allowing downhill flow of Na+ from the endosome into the cytosol. While any K+ selective ionophore can promote the K+ specific influx, the ideal K+ ionophore will also exchange influxed K+ for an osmotically inactive proton (H+) in order to prevent buildup of an electrical potential that would rapidly halt K+ influx. The only ionophore that catalyzes this exchange of K+ for H+ efficiently is nigericin. We demonstrate here that ligand-targeted delivery of nigericin into endosomes that contain an otherwise impermeable fluorescent dye can augment release of the dye into the cell cytosol via swelling/bursting of the entrapping endosomes. We further show that nigericin-facilitated escape of a folate-targeted luciferase siRNA conjugate from its entrapping endosomes promotes rapid suppression of the intended luciferase reporter gene. Taken together, we propose that ionophore-catalyzed entry of K+ into endosomal compartments can promote the release of otherwise impermeable contents from their encapsulating endosomes.


Assuntos
Endossomos/efeitos dos fármacos , Hidrogênio/metabolismo , Ionóforos/farmacologia , Nigericina/farmacologia , Potássio/metabolismo , Animais , Linhagem Celular Tumoral , Citosol/metabolismo , Endocitose , Endossomos/metabolismo , Corantes Fluorescentes/metabolismo , Humanos , Camundongos , Osmose , Células RAW 264.7 , RNA Interferente Pequeno/metabolismo , Sódio/metabolismo
6.
Oncotarget ; 8(57): 96470-96471, 2017 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-29228541
7.
Adv Cancer Res ; 135: 53-118, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28882225

RESUMO

The discovery of the microRNAs, lin-4 and let-7 as critical mediators of normal development in Caenorhabditis elegans and their conservation throughout evolution has spearheaded research toward identifying novel roles of microRNAs in other cellular processes. To accurately elucidate these fundamental functions, especially in the context of an intact organism, various microRNA transgenic models have been generated and evaluated. Transgenic C. elegans (worms), Drosophila melanogaster (flies), Danio rerio (zebrafish), and Mus musculus (mouse) have contributed immensely toward uncovering the roles of multiple microRNAs in cellular processes such as proliferation, differentiation, and apoptosis, pathways that are severely altered in human diseases such as cancer. The simple model organisms, C. elegans, D. melanogaster, and D. rerio, do not develop cancers but have proved to be convenient systesm in microRNA research, especially in characterizing the microRNA biogenesis machinery which is often dysregulated during human tumorigenesis. The microRNA-dependent events delineated via these simple in vivo systems have been further verified in vitro, and in more complex models of cancers, such as M. musculus. The focus of this review is to provide an overview of the important contributions made in the microRNA field using model organisms. The simple model systems provided the basis for the importance of microRNAs in normal cellular physiology, while the more complex animal systems provided evidence for the role of microRNAs dysregulation in cancers. Highlights include an overview of the various strategies used to generate transgenic organisms and a review of the use of transgenic mice for evaluating preclinical efficacy of microRNA-based cancer therapeutics.


Assuntos
MicroRNAs/genética , Animais , Animais Geneticamente Modificados/genética , Carcinogênese/genética , Humanos , Modelos Animais , Neoplasias/genética
8.
Sci Transl Med ; 9(401)2017 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-28768807

RESUMO

MicroRNAs are small RNAs that negatively regulate gene expression posttranscriptionally. Because changes in microRNA expression can promote or maintain disease states, microRNA-based therapeutics are being evaluated extensively. Unfortunately, the therapeutic potential of microRNA replacement is limited by deficient delivery vehicles. In this work, microRNAs are delivered in the absence of a protective vehicle. The method relies on direct attachment of microRNAs to folate (FolamiR), which mediates delivery of the conjugated microRNA into cells that overexpress the folate receptor. We show that the tumor-suppressive FolamiR, FolamiR-34a, is quickly taken up both by triple-negative breast cancer cells in vitro and in vivo and by tumors in an autochthonous model of lung cancer and slows their progression. This method delivers microRNAs directly to tumors in vivo without the use of toxic vehicles, representing an advance in the development of nontoxic, cancer-targeted therapeutics.


Assuntos
Ácido Fólico/metabolismo , Técnicas de Transferência de Genes , MicroRNAs/administração & dosagem , Células A549 , Animais , Neoplasias da Mama/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Feminino , Marcação de Genes , Humanos , Imunocompetência , Ligantes , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Camundongos , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
9.
JCI Insight ; 2(5): e90487, 2017 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-28289710

RESUMO

Loss of LKB1 activity is prevalent in KRAS mutant lung adenocarcinoma and promotes aggressive and treatment-resistant tumors. Previous studies have shown that LKB1 is a negative regulator of the focal adhesion kinase (FAK), but in vivo studies testing the efficacy of FAK inhibition in LKB1 mutant cancers are lacking. Here, we took a pharmacologic approach to show that FAK inhibition is an effective early-treatment strategy for this high-risk molecular subtype. We established a lenti-Cre-induced Kras and Lkb1 mutant genetically engineered mouse model (KLLenti) that develops 100% lung adenocarcinoma and showed that high spatiotemporal FAK activation occurs in collective invasive cells that are surrounded by high levels of collagen. Modeling invasion in 3D, loss of Lkb1, but not p53, was sufficient to drive collective invasion and collagen alignment that was highly sensitive to FAK inhibition. Treatment of early, stage-matched KLLenti tumors with FAK inhibitor monotherapy resulted in a striking effect on tumor progression, invasion, and tumor-associated collagen. Chronic treatment extended survival and impeded local lymph node spread. Lastly, we identified focally upregulated FAK and collagen-associated collective invasion in KRAS and LKB1 comutated human lung adenocarcinoma patients. Our results suggest that patients with LKB1 mutant tumors should be stratified for early treatment with FAK inhibitors.


Assuntos
Adenocarcinoma/genética , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Neoplasias Pulmonares/genética , Mutação , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Transdução de Sinais , Animais , Ativação Enzimática , Proteína-Tirosina Quinases de Adesão Focal/antagonistas & inibidores , Humanos , Camundongos , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo
10.
Bio Protoc ; 6(21)2016 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-28573164

RESUMO

The SRB assay has been used since its development in 1990 (Skehan et al., 1990) to inexpensively conduct various screening assays to investigate cytotoxicity in cell based studies (Vichai and Kirtikara, 2006). This method relies on the property of SRB, which binds stoichiometrically to proteins under mild acidic conditions and then can be extracted using basic conditions; thus, the amount of bound dye can be used as a proxy for cell mass, which can then be extrapolated to measure cell proliferation. The protocol can be divided into four main steps: preparation of treatment, incubation of cells with treatment of choice, cell fixation and SRB staining, and absorbance measurement. This assay is limited to manual or semiautomatic screening, and can be used in an efficient and sensitive manner to test chemotherapeutic drugs or small molecules in adherent cells. It also has applications in evaluating the effects of gene expression modulation (knockdown, gene expression upregulation), as well as to study the effects of miRNA replacement on cell proliferation (Kasinski et al., 2015).

11.
Cancers (Basel) ; 7(3): 1388-405, 2015 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-26226002

RESUMO

Recent progress in microRNA (miRNA) therapeutics has been strongly dependent on multiple seminal discoveries in the area of miRNA biology during the past two decades. In this review, we focus on the historical discoveries that collectively led to transitioning miRNAs into the clinic. We highlight the pivotal studies that identified the first miRNAs in Caenorhabditis elegans to the more recent reports that have fueled the quest to understand the use of miRNAs as markers for cancer diagnosis and prognosis. In addition, we provide insights as to how unraveling basic miRNA biology has provided a solid foundation for advancing miRNAs, such as miR-34a, therapeutically. We conclude with a brief examination of the current challenges that still need to be addressed to accelerate the path of miRNAs to the clinic: including delivery vehicles, miRNA- and delivery-associated toxicity, dosage, and off target effects.

12.
J Hematol Oncol ; 8: 31, 2015 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-25888285

RESUMO

From its discovery as an adaptive bacterial and archaea immune system, the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system has quickly been developed into a powerful and groundbreaking programmable nuclease technology for the global and precise editing of the genome in cells. This system allows for comprehensive unbiased functional studies and is already advancing the field by revealing genes that have previously unknown roles in disease processes. In this review, we examine and compare recently developed CRISPR-Cas platforms for global genome editing and examine the advancements these platforms have made in guide RNA design, guide RNA/Cas9 interaction, on-target specificity, and target sequence selection. We also explore some of the exciting therapeutic potentials of the CRISPR-Cas technology as well as some of the innovative new uses of this technology beyond genome editing.


Assuntos
Sistemas CRISPR-Cas , Engenharia Genética/métodos , RNA , Animais , Humanos
13.
Environ Mol Mutagen ; 56(3): 277-85, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25482136

RESUMO

Genetic toxicity tests currently used to identify and characterize potential human mutagens and carcinogens rely on measurements of primary DNA damage, gene mutation, and chromosome damage in vitro and in rodents. The International Life Sciences Institute Health and Environmental Sciences Institute (ILSI-HESI) Committee on the Relevance and Follow-up of Positive Results in In Vitro Genetic Toxicity Testing held an April 2012 Workshop in Washington, DC, to consider the impact of new understanding of biology and new technologies on the identification and characterization of genotoxic substances, and to identify new approaches to inform more accurate human risk assessment for genetic and carcinogenic effects. Workshop organizers and speakers were from industry, academe, and government. The Workshop focused on biological effects and technologies that would potentially yield the most useful information for evaluating human risk of genetic damage. Also addressed was the impact that improved understanding of biology and availability of new techniques might have on genetic toxicology practices. Workshop topics included (1) alternative experimental models to improve genetic toxicity testing, (2) Biomarkers of epigenetic changes and their applicability to genetic toxicology, and (3) new technologies and approaches. The ability of these new tests and technologies to be developed into tests to identify and characterize genotoxic agents; to serve as a bridge between in vitro and in vivo rodent, or preferably human, data; or to be used to provide dose response information for quantitative risk assessment was also addressed. A summary of the workshop and links to the scientific presentations are provided.


Assuntos
Testes de Mutagenicidade/métodos , Mutagênicos/toxicidade , Animais , District of Columbia , Epigênese Genética/efeitos dos fármacos , Genômica/métodos , Humanos , Medição de Risco
14.
Curr Biol ; 24(16): R762-76, 2014 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-25137592

RESUMO

Malignant neoplasms are consistently among the top four leading causes of death in all age groups in the United States, despite a concerted effort toward developing novel therapeutic approaches. Our understanding of and therapeutic strategy for treating each of these neoplastic diseases have been improved through decades of research on the genetics, signaling pathways, and cellular biology that govern tumor cell initiation, progression and maintenance. Much of this work has concentrated on post-translational modifications and abnormalities at the DNA level, including point mutations, amplifications/deletions, and chromosomal translocations, and how these aberrant events affect the expression and function of protein-coding genes. Only recently has a novel class of conserved gene regulatory molecules been identified as a major contributor to malignant neoplastic disease. This review focuses on how these small non-coding RNA molecules, termed microRNAs (miRNAs), can function as oncogenes or tumor suppressors, and how the misexpression of miRNAs and dysregulation of factors that regulate miRNAs contribute to the tumorigenic process. Specific focus is given to more recently discovered regulatory mechanisms that go awry in cancer, and how these changes alter miRNA expression, processing, and function.


Assuntos
Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , MicroRNAs/genética , Neoplasias/genética , Oncogenes , MicroRNAs/metabolismo
15.
Mol Cell Biol ; 33(11): 2252-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23530055

RESUMO

Cellular processes are tightly controlled through well-coordinated signaling networks that respond to conflicting cues, such as reactive oxygen species (ROS), endoplasmic reticulum (ER) stress signals, and survival factors to ensure proper cell function. We report here a direct interaction between inhibitor of κB kinase (IKK) and apoptosis signal-regulating kinase 1 (ASK1), unveiling a critical node at the junction of survival, inflammation, and stress signaling networks. IKK can be activated by growth factor stimulation or tumor necrosis factor alpha engagement. IKK forms a complex with and phosphorylates ASK1 at a sensor site, Ser967, leading to the recruitment of 14-3-3, counteracts stress signal-triggered ASK1 activation, and suppresses ASK1-mediated functions. An inhibitory role of IKK in JNK signaling has been previously reported to depend on NF-κB-mediated gene expression. Our data suggest that IKK has a dual role: a transcription-dependent and a transcription-independent action in controlling the ASK1-JNK axis, coupling IKK to ROS and ER stress response. Direct phosphorylation of ASK1 by IKK also defines a novel IKK phosphorylation motif. Because of the intimate involvement of ASK1 in diverse diseases, the IKK/ASK1 interface offers a promising target for therapeutic development.


Assuntos
Quinase I-kappa B/metabolismo , MAP Quinase Quinase Quinase 5/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Apoptose/fisiologia , Células COS/efeitos dos fármacos , Células COS/metabolismo , Cromonas/farmacologia , Peróxido de Hidrogênio/farmacologia , Quinase I-kappa B/genética , MAP Quinase Quinase Quinase 5/genética , Camundongos , Morfolinas/farmacologia , Neuritos/fisiologia , Células PC12 , Fosforilação , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Serina/metabolismo , Transdução de Sinais
16.
Bio Protoc ; 3(15)2013 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-27239482

RESUMO

Although in vivo models are excellent for assessing various facets of whole organism physiology, pathology, and overall response to treatments, evaluating basic cellular functions, and molecular events in mammalian model systems is challenging. It is therefore advantageous to perform these studies in a refined and less costly setting. One approach involves utilizing cells derived from the model under evaluation. The approach to generate such cells varies based on the cell of origin and often the genetics of the cell. Here we describe the steps involved in generating epithelial cells from the lungs of KrasLSL-G12D/+; p53LSL-R172/+ mice (Kasinski and Slack, 2012). These mice develop aggressive lung adenocarcinoma following cre-recombinase dependent removal of a stop cassette in the transgenes and subsequent expression of Kra-G12D and p53R172 . While this protocol may be useful for the generation of epithelial lines from other genetic backgrounds, it should be noted that the Kras; p53 cell line generated here is capable of proliferating in culture without any additional genetic manipulation that is often needed for less aggressive backgrounds.

18.
Cancer Res ; 72(21): 5576-87, 2012 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-22964582

RESUMO

Lung cancer is the leading cause of cancer deaths worldwide, and current therapies fail to treat this disease in the vast majority of cases. The RAS and p53 pathways are two of the most frequently altered pathways in lung cancers, with such alterations resulting in loss of responsiveness to current therapies and decreased patient survival. The microRNA-34 (mir-34) gene family members are downstream transcriptional targets of p53, and miR-34 expression is reduced in p53 mutant tumors; thus, we hypothesized that treating mutant Kras;p53 tumors with miR-34 would represent a powerful new therapeutic to suppress lung tumorigenesis. To this end we examined the therapeutically resistant Kras(LSL-G12D)(/+);Trp53(LSL-R172H)(/+) mouse lung cancer model. We characterized tumor progression in these mice following lung-specific transgene activation and found tumors as early as 10 weeks postactivation, and severe lung inflammation by 22 weeks. Tumors harvested from these lungs have elevated levels of oncogenic miRNAs, miR-21 and miR-155; are deficient for p53-regulated miRNAs; and have heightened expression of miR-34 target genes, such as Met and Bcl-2. In the presence of exogenous miR-34, epithelial cells derived from these tumors show reduced proliferation and invasion. In vivo treatment with miR-34a prevented tumor formation and progression in Kras(LSL-G12D)(/+);Trp53(LSL-R172H)(/+) mice. Animals infected with mir-34a-expressing lentivirus at the same time as transgene activation had little to no evidence of tumorigenesis, and lentivirus-induced miR-34a also prevented further progression of preformed tumors. These data support the use of miR-34 as a lung tumor-preventative and tumor-static agent.


Assuntos
Adenocarcinoma/genética , Terapia Genética/métodos , Neoplasias Pulmonares/genética , MicroRNAs/genética , Adenocarcinoma/terapia , Adenocarcinoma de Pulmão , Adenoviridae/genética , Animais , Transformação Celular Neoplásica/genética , Modelos Animais de Doenças , Progressão da Doença , Vetores Genéticos , Imuno-Histoquímica , Neoplasias Pulmonares/terapia , Camundongos , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
20.
Nat Rev Cancer ; 11(12): 849-64, 2011 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-22113163

RESUMO

In normal cells multiple microRNAs (miRNAs) converge to maintain a proper balance of various processes, including proliferation, differentiation and cell death. miRNA dysregulation can have profound cellular consequences, especially because individual miRNAs can bind to and regulate multiple mRNAs. In cancer, the loss of tumour-suppressive miRNAs enhances the expression of target oncogenes, whereas increased expression of oncogenic miRNAs (known as oncomirs) can repress target tumour suppressor genes. This realization has resulted in a quest to understand the pathways that are regulated by these miRNAs using in vivo model systems, and to comprehend the feasibility of targeting oncogenic miRNAs and restoring tumour-suppressive miRNAs for cancer therapy. Here we discuss progress in using mouse models to understand the roles of miRNAs in cancer and the potential for manipulating miRNAs for cancer therapy as these molecules make their way towards clinical trials.


Assuntos
Epigênese Genética , MicroRNAs/fisiologia , Neoplasias/genética , Animais , Humanos , Camundongos , MicroRNAs/antagonistas & inibidores , Metástase Neoplásica , Neoplasias/terapia , Polimorfismo de Nucleotídeo Único
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