ArticleNature cell biology2012
Synthetic lethality between Rb, p53 and Dicer or miR-17-92 in retinal progenitors suppresses retinoblastoma formation.
Article in Nature cell biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
58 citing papers in PubMed, 79 citations in OpenAlex.
- Advances in synthetic lethality modalities for glioblastoma multiforme.Open medicine (Warsaw, Poland) · 2024Review
- Exploiting Cancer Synthetic Lethality in Cancer-Lessons Learnt from PARP Inhibitors.Cancer treatment and research · 2023Article
- Are We Moving the Needle for Patients withCancers · 2022Review
- Retinoblastoma tumor cell proliferation is negatively associated with an immune gene expression signature and increased immune cells.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- Cross-species identification of PIP5K1-, splicing- and ubiquitin-related pathways as potential targets for RB1-deficient cells.PLoS genetics · 2021Article
- Review
- MIR17HG polymorphism (rs7318578) is associated with liver cancer risk in the Chinese Han population.Bioscience reports · 2020Article
- Inhibition of miR-1193 leads to synthetic lethality in glioblastoma multiforme cells deficient of DNA-PKcs.Cell death & disease · 2020Article
- Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study.Acta neuropathologica · 2020Article
- miR-133a-3p promotes apoptosis and induces cell cycle arrest by targeting CREB1 in retinoblastoma.Archives of medical science : AMS · 2020Article
- Biomarkers in retinoblastoma.International journal of ophthalmology · 2020Review
- Expression profiles and prognostic value of miRNAs in retinoblastoma.Journal of cancer research and clinical oncology · 2019Review
- Tumor Suppressor miR-184 Enhances Chemosensitivity by Directly Inhibiting SLC7A5 in Retinoblastoma.Frontiers in oncology · 2019Article
- Non-Coding RNAs in Pediatric Solid Tumors.Frontiers in genetics · 2019Review
- Identification of highly penetrant Rb-related synthetic lethal interactions in triple negative breast cancer.Oncogene · 2018Article
- Synthetic lethal therapies for cancer: what's next after PARP inhibitors?Nature reviews. Clinical oncology · 2018Review
- DNA Methylomes Reveal Biological Networks Involved in Human Eye Development, Functions and Associated Disorders.Scientific reports · 2017Article
- [Regulation of microRNA-17-92 cluster on bone development, remodeling, and metabolism].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2017Review
- [Value of serum miR-17-92 cluster in diagnosis of retinoblastoma].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2017Article
- Retinoblastoma cells activate the AKT pathway and are vulnerable to the PI3K/mTOR inhibitor NVP-BEZ235.Oncotarget · 2017Article
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13 authors at 6 institutions in 4 countries.
Funding
Abstract
Synthetic lethality is a promising strategy for specific targeting of cancer cells that carry mutations that are absent in normal cells. This approach may help overcome the challenge associated with targeting dysfunctional tumour suppressors, such as p53 and Rb (refs 1, 2). Here we show that Dicer1 targeting prevents retinoblastoma formation in mice by synthetic lethality with combined inactivation of p53 and Rb. Although Dicer1 functions as a haploinsufficient tumour suppressor, its complete loss of function is selected against during tumorigenesis(3-5). We show that Dicer1 deficiency is tolerated in Rb-deficient retinal progenitor cells harbouring an intact p53 pathway, but not in the absence of p53. This synthetic lethality is mediated by the oncogenic miR-17-92 cluster because its deletion phenocopies Dicer1 loss in this context. miR-17-92 inactivation suppresses retinoblastoma formation in mice and co-silencing of miR-17/20a and p53 cooperatively decreases the viability of human retinoblastoma cells. These data provide an explanation for the selective pressure against loss of Dicer1 during tumorigenesis and a proof-of-concept that targeting miRNAs may potentially represent a general approach for synthetic lethal targeting of cancer cells that harbour specific cancer-inducing genotypes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.