Evidence map›Paper›PMID 32361246›Full record

ArticleEBioMedicine2020

Radiation-induced extracellular vesicle (EV) release of miR-603 promotes IGF1-mediated stem cell state in glioblastomas.

Valya Ramakrishnan, Beibei Xu, Johnny Akers, Thien Nguyen, Jun Ma, Sanjay Dhawan, Jianfang Ning, Ying Mao, Wei Hua, Efrosini Kokkoli and 3 more

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

Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 8% 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

47 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Research on exosomes in cancer multidrug resistance and clinical translation.Extracellular vesicles and circulating nucleic acids · 2026
    Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. The role of IGF/IGF-1R signaling in the regulation of cancer stem cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024
    Review
  17. Review
  18. Review
  19. Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 6 institutions in 2 countries.

Valya RamakrishnanDepartment of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA.
Beibei XuDepartment of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA.
Johnny AkersVisiCELL Medical Inc., San Diego, CA 92121, USA.
Thien NguyenSchool of Medicine, University of California, Los Angeles, CA 90095, USA.
Jun MaDepartment of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA.
Sanjay DhawanDepartment of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA.
Jianfang NingDepartment of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA.
Ying MaoDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
Wei HuaDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
Efrosini KokkoliDepartment of Chemical and Biomolecular Engineering, Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
Frank FurnariLudwig Institute of Cancer Research, University of California, San Diego, CA 92093, USA.
Bob S CarterDepartment of Neurosurgery, Massachusetts General Hospital, Boston, MA 02114, USA.
Clark C ChenDepartment of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: ccchen@umn.edu.
University of Minnesota · USFudan University · CNJohns Hopkins University · USMassachusetts General Hospital · USUniversity of California, Los Angeles · USUniversity of California San Diego · US

Funding

Genotypic Interactions in Brain Cancer HeterogeneityR01NS080939 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FURNARI, FRANK · 2012 to 2022
$3.5M
Development of Quantitative Deuterium MRS Imaging for Human Brain Tumor Application at Ultrahigh FieldR01CA240953 · NCI · UNIVERSITY OF MINNESOTA · PI CHEN, WEI, LIANG, ZHI-PEI · 2019 to 2025
$2.7M
Targeting Mechanisms of Acquired Temozolomide Resistance in GlioblastomaR01NS097649 · NINDS · UNIVERSITY OF MINNESOTA · PI CHEN, CLARK CHIN-CHUNG · 2016 to 2021
$1.7M
High-throughput single-cell sorting and kinetic analysis of secreted particlesR44GM128223 · NIGMS · NANOCELLECT BIOMEDICAL, INC. · PI CHEN, CLARK CHIN-CHUNG, LO, YU-HWA · 2017 to 2018
$1.6M
NCI NIH HHS R01 CA240953NIGMS NIH HHS R44 GM128223NINDS NIH HHS R01 NS080939NINDS NIH HHS R01 NS097649
6 · The paper itself

Abstract

backgroundRecurrence after radiation therapy is nearly universal for glioblastomas, the most common form of adult brain cancer. The study aims to define clinically pertinent mechanisms underlying this recurrence.

methodsmicroRNA (miRNA) profiling was performed using matched pre- and post-radiation treatment glioblastoma specimens from the same patients. All specimens harbored unmethylated O

findingsWhile nearly all miRNAs remained unchanged after treatment, decreased levels of few, select miRNAs in the post-treatment specimens were observed, the most notable of which involved miR-603. Unbiased profiling of miR-603 targets revealed insulin-like growth factor 1 (IGF1) and IGF1 receptor (IGF1R). Ionizing radiation (IR) induced cellular export of miR-603 through extracellular vesicle (EV) release, thereby de-repressing IGF1 and IGF1R. This de-repression, in turn, promoted cancer stem-cell (CSC) state and acquired radiation resistance in glioblastomas. Export of miR-603 additionally de-repressed MGMT, a DNA repair protein responsible for detoxifying DNA alkylating agents, to promote cross-resistance to these agents. Ectopic miR-603 expression overwhelmed cellular capacity for miR-603 export and synergized with the tumoricidal effects of IR and DNA alkylating agents.

interpretationProfiling of matched pre- and post-treatment glioblastoma specimens revealed altered homeostasis of select miRNAs in response to radiation. Radiation-induced EV export of miR-603 simultaneously promoted the CSC state and up-regulated DNA repair to promote acquired resistance. These effects were abolished by exogenous miR-603 expression, suggesting potential for clinical translation.

fundingNIH 1R01NS097649-01, 9R44GM128223-02, 1R01CA240953-01, the Doris Duke Charitable Foundation Clinical Scientist Development Award, The Sontag Foundation Distinguished Scientist Award, the Kimmel Scholar Award, and BWF 1006774.01 (C.C.C).

Indexed as

AnimalsBrain NeoplasmsCell Line, TumorCell SurvivalDNA Modification MethylasesDNA RepairDNA Repair EnzymesExtracellular VesiclesGamma RaysGene Expression Regulation, NeoplasticGlioblastomaHistonesHumansInsulin-Like Growth Factor IIsocitrate DehydrogenaseMaleDNA Modification MethylasesDNA Repair EnzymesH2AX protein, humanHistonesIGF1 protein, humanIGF1R protein, humanInsulin-Like Growth Factor IIsocitrate DehydrogenaseMGMT protein, humanMicroRNAsMIRN603 microRNA, humanReceptor, IGF Type 1Tumor Suppressor ProteinsAcquired radiation resistanceExtracellular vesiclesGlioblastoma stem-cell stateIGF1MGMTmiR-603

Identifiers

PMID32361246
PMCPMC7195524
OpenAlexW3022324472

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.