Activating PTEN Tumor Suppressor Expression with the CRISPR/dCas9 System

Moses, Colette; Nugent, Fiona; Waryah, Charlene Babra; García-Bloj, Benjamin; Harvey, Alan R.; Blancafort, Pilar

doi:10.1016/j.omtn.2018.12.003

Cited by 81 publications

(72 citation statements)

References 103 publications

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“…The present study verified that PTEN was a direct target of miR-208a-3p in OS cells. Downregulation of PTEN, a well-known tumor suppressor protein, may result in tumor progression (36,37). As a tumor suppressor, PTEN has been associated with several biological processes, including maintenance of genomic stability, cell survival, migration, proliferation and metabolism (38).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑208a‑3p promotes osteosarcoma progression via targeting PTEN

Wang

et al. 2020

Exp Ther Med

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Osteosarcoma (OS) is a malignant bone tumor with a poor prognosis. Accumulated evidence has suggested that microRNAs (miRNAs/miRs) may function as either oncogenes or tumor suppressors, which are associated with tumorigenesis and the progression of different types of cancer. In the present study, the role of miR-208a-3p in OS was investigated. The expression levels of miR-208a-3p in OS tissues and cell lines were determined via reverse transcription-quantitative PCR (RT-qPCR). MTT and colony formation assays were performed to verify the proliferation rate of OS cells. In addition, the effects of miR-208a-3p on the migration and invasion of OS cells were revealed using wound-healing and Transwell assays, respectively. Furthermore, the association between miR-208a-3p and phosphatase and tensin homolog (PTEN) 3'-untranslated region was determined via luciferase reporter assays, western blot and RT-qPCR analysis. The results indicated that miR-208a-3p was upregulated in OS tissues and cell lines compared with adjacent normal tissues and human osteoblastic cells, respectively. miR-208a-3p overexpression promoted and miR-208a-3p knockdown inhibited OS cells proliferation and metastatic potential. Additionally, PTEN was validated as a direct target of miR-208a-3p and its expression was negatively associate with that of miR-208a-3p in OS cells. Taken together, these results may suggest that miR-208a-3p promoted OS cells proliferation and metastatic potential via targeting PTEN. Therefore, miR-208a-3p may be considered as a diagnostic biomarker for OS.

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Section: Discussionmentioning

confidence: 99%

MicroRNA‑208a‑3p promotes osteosarcoma progression via targeting PTEN

Wang

et al. 2020

Exp Ther Med

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“…Outras maneiras possíveis de utilizar o CRISPR-Cas9 é por meio da edição de genes supressores de tumores ou em oncogenes. O estudo de Moses et al 41 demostrou a capacidade do sistema CRISPR-Cas de realizar a ativação da PTEN, uma proteína supressora de tumor essencial, que quando silenciada, promove comportamento metastático e resistência à terapia de cânceres altamente agressivos. Diante de tantas possibilidades, a utilização desse sistema tão complexo traz grandes perspectivas para a terapia genética.…”

Section: Discussionunclassified

A Tecnologia De Crispr-Cas9 Na Terapia Gênica Do Câncer De Pulmão

Alcantara

Lima

Barbosa

et al. 2019

RBMC

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O presente estudo objetivou avaliar a possibilidade do CRISPR-Cas9 na terapia gênica do câncer de pulmão, por meio do conhecimento do mecanismo da CRISPR-Cas e da sua utilização no tratamento do câncer de pulmão. Trata-se de uma revisão de literatura de aspecto descritivo. Foram excluídas as publicações e artigos repetidos que não eram relacionadas ao tema, totalizando 22 referências e tendo como 41 referências que constituem o presente trabalho, retiradas no site da National Center for Biotecnology Information (NCBI), na base de dados PubMed. Foram utilizados os descritores: CRISPR/Cas9, Lung Cancer, Gene therapy, gene edition, adaptive immunity, após foram catalogadas e submetidas a análise. Estudos de artigos referentes à terapia gênica, através da utilização do CRISPR-Cas9, demonstraram diversas possibilidades de utilização do sistema para o tratamento de tumores, indicando um possível tratamento do câncer de pulmão pelo sistema CRISPR-Cas9, dependendo somente de pesquisa e estudos. O sistema CRISPR-Cas9 pode ser considerado a tecnologia do século, por proporcionar uma plataforma adequada para o desenvolvimento de pesquisas relacionadas aos adenocarcinomas em condições in vivo e in vitro e trazer diversas possibilidades para tratar o câncer de pulmão com base na terapia gênica.

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“…In addition, large deletions spanning kilobases and complex rearrangements as unintended consequences of on-target activity have been reported in several instances (71,72), highlighting a major safety issue for clinical applications of DSB-inducing CRISPR therapy. Other variations of Cas9, such as catalytically inactive endonuclease dead Cas9 (dCas9) in which the nuclease domains are deactivated, may provide therapeutic utility while mitigating the risks of DSBs (73). dCas9 can transiently manipulate expression of specific genes without introducing DSBs through fusion of transcriptional activating or repressing domains or proteins to the DNA-binding effector (74).…”

Section: Dna-damage Toxicitymentioning

confidence: 99%

CRISPR Gene Therapy: Applications, Limitations, and Implications for the Future

2020

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A series of recent discoveries harnessing the adaptive immune system of prokaryotes to perform targeted genome editing is having a transformative influence across the biological sciences. The discovery of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (Cas) proteins has expanded the applications of genetic research in thousands of laboratories across the globe and is redefining our approach to gene therapy. Traditional gene therapy has raised some concerns, as its reliance on viral vector delivery of therapeutic transgenes can cause both insertional oncogenesis and immunogenic toxicity. While viral vectors remain a key delivery vehicle, CRISPR technology provides a relatively simple and efficient alternative for site-specific gene editing, obliviating some concerns raised by traditional gene therapy. Although it has apparent advantages, CRISPR/Cas9 brings its own set of limitations which must be addressed for safe and efficient clinical translation. This review focuses on the evolution of gene therapy and the role of CRISPR in shifting the gene therapy paradigm. We review the emerging data of recent gene therapy trials and consider the best strategy to move forward with this powerful but still relatively new technology.

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Activating PTEN Tumor Suppressor Expression with the CRISPR/dCas9 System

Cited by 81 publications

References 103 publications

MicroRNA‑208a‑3p promotes osteosarcoma progression via targeting PTEN

MicroRNA‑208a‑3p promotes osteosarcoma progression via targeting PTEN

A Tecnologia De Crispr-Cas9 Na Terapia Gênica Do Câncer De Pulmão

CRISPR Gene Therapy: Applications, Limitations, and Implications for the Future

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