Evidence map›Paper›PMID 28153089›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2017

Genome Editing Reveals Glioblastoma Addiction to MicroRNA-10b.

Rachid El Fatimy, Shruthi Subramanian, Erik J Uhlmann, Anna M Krichevsky

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
3.6field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

65 citing papers in PubMed, 98 citations in OpenAlex.

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5 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Rachid El FatimyDepartment of Neurology, Ann Romney Center for Neurologic Diseases, Initiative for RNA Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Shruthi SubramanianDepartment of Neurology, Ann Romney Center for Neurologic Diseases, Initiative for RNA Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Erik J UhlmannDepartment of Neurology, Ann Romney Center for Neurologic Diseases, Initiative for RNA Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Anna M KrichevskyDepartment of Neurology, Ann Romney Center for Neurologic Diseases, Initiative for RNA Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: akrichevsky@rics.bwh.harvard.edu.
Brigham and Women's Hospital · USHarvard University · US

Funding

Validation of microRNA Targets in GliomaR01CA138734 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI KRICHEVSKY, ANNA M. · 2010 to 2014
$1.7M
NCI NIH HHS R01 CA138734
6 · The paper itself

Abstract

Glioblastoma (GBM) brain tumor remains among the most lethal and incurable human diseases. Oncogenic microRNA-10b (miR-10b) is strongly and universally upregulated in GBM, and its inhibition by antisense oligonucleotides (ASOs) reduces the growth of heterogeneous glioma cells; therefore, miR-10b represents a unique therapeutic target for GBM. Here we explored the effects of miR-10b gene editing on GBM. Using the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system, we investigated effects of miR-10b gene editing on the growth of cultured human glioma cells, tumor-initiating stem-like cells, and mouse GBM xenografts, as well as the oncogene-induced transformation of normal astrocytes. We show that GBM is strictly "addicted" to miR-10b and that miR-10b gene ablation is lethal for glioma cell cultures and established intracranial tumors. miR-10b loss-of-function mutations lead to the death of glioma, but not other cancer cell lines. We have not detected escaped proliferative clones of GBM cells edited in the miR-10b locus. Finally, neoplastic transformation of normal astrocytes was abolished by the miR-10b-editing vectors. This study demonstrates the feasibility of gene editing for brain tumors in vivo and suggests virus-mediated miR-10b gene ablation as a promising therapeutic approach that permanently eliminates the key regulator essential for tumor growth and survival.

Indexed as

Gene EditingAnimalsAstrocytesBase SequenceBrain NeoplasmsCell Line, TumorCell ProliferationCell SurvivalCell Transformation, NeoplasticCRISPR-Cas SystemsDisease Models, AnimalGene Expression Regulation, NeoplasticGlioblastomaHumansMiceMicroRNAsMicroRNAsMIRN10 microRNA, humanRNA, Guide, CRISPR-Cas Systemsbrain tumorcancerCRISPR-Cas9gene editinggenome editingglioblastomamicroRNA-10bncRNAorthotopic animal modelstherapy

Identifiers

PMID28153089
PMCPMC5368404
OpenAlexW2571691893

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.