Evidence map›Paper›PMID 33088424›Full record

ArticleOncotarget2020

Exosomes secreted under hypoxia enhance stemness in Ewing's sarcoma through miR-210 delivery.

Matthew J Kling, Nagendra K Chaturvedi, Varun Kesherwani, Don W Coulter, Timothy R McGuire, J Graham Sharp, Shantaram S Joshi

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

Article in Oncotarget, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.0field-weighted citation impact, top 25% 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

21 citing papers in PubMed, 26 citations in OpenAlex.

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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

7 authors at 3 institutions in 1 country.

Matthew J KlingDepartment of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA.
Nagendra K ChaturvediDepartment of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA.
Varun KesherwaniDepartment of Biomedical Sciences, Creighton University, Omaha, NE, USA.
Don W CoulterDepartment of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA.
Timothy R McGuireDepartment of Pharmacy Practice and Science, University of Nebraska Medical Center, Omaha, NE, USA.
J Graham SharpDepartment of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA.
Shantaram S JoshiDepartment of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA.
University of Nebraska Medical Center · USChildren's Hospital & Medical Center · USCreighton University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Intercellular communication between tumor cells within the hypoxic microenvironment promote aggressiveness and poor patient prognoses for reasons that remain unclear. Here we show that hypoxic Ewing's sarcoma (EWS) cells release exosomes that promote sphere formation, a stem-like phenotype, in EWS cells by enhancing survival. Analysis of the hypoxic exosomal miRNA cargo identified a HIF-1α regulated miRNA, miR-210, as a potential mediator of sphere formation in cells exposed to hypoxic exosomes. Knockdown of HIF-1α in hypoxic EWS cells led to decreased exosomal miR-210 levels and reduced the capacity of hypoxic exosomes to form spheres. Inhibition of miR-210 in hypoxic spheres attenuated sphere formation and overexpression of miR-210 in normoxic spheres significantly enhanced the number of EWS spheres. Our results indicate that hypoxic exosomal miR-210 targets the proapoptotic protein CASP8AP2 in recipient cells. Moreover, the suppression of CASP8AP2 led to a reduction in apoptotic cells and increased sphere formation. Together, the findings in this study suggest that hypoxic exosomes promote stemness in EWS cells by delivering enriched miR-210 that is capable of down-regulating apoptotic pathways, resulting in the survival of cells with increased sphere formation. Future studies will further investigate the effects of EWS derived exosomal miRNAs on target genes and the role these interactions play in driving aggressiveness in hypoxic EWS tumors.

Indexed as

Ewing’s sarcomaexosomeshypoxiamiR-210stemness

Identifiers

PMID33088424
PMCPMC7546758
OpenAlexW3092229267

What OpenQuestion holds

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LicenceCC BY
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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.