Evidence map›Paper›PMID 30487062›Full record

ArticleEBioMedicine2018

Exosomal miRNA confers chemo resistance via targeting Cav1/p-gp/M2-type macrophage axis in ovarian cancer.

Pinar Kanlikilicer, Recep Bayraktar, Merve Denizli, Mohammed H Rashed, Cristina Ivan, Burcu Aslan, Rahul Mitra, Kubra Karagoz, Emine Bayraktar, Xinna Zhang and 10 more

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

Article in EBioMedicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 150 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
150citing papers in PubMed, 3 pooled it
9.5field-weighted citation impact, top 1% 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

150 citing papers in PubMed, 3 syntheses or guidelines pooled it, 216 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 3 institutions in 2 countries.

Pinar KanlikilicerDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Recep BayraktarDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Merve DenizliDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Mohammed H RashedDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Cristina IvanCenter for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Burcu AslanDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Rahul MitraCenter for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Kubra KaragozRutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA.
Emine BayraktarDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Xinna ZhangCenter for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Cristian Rodriguez-AguayoDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Amr Ahmed El-ArabeyDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Nermin KahramanDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Seyda BaydoganDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Ozgur OzkayarHacettepe University, Ankara, Turkey.
Michael L GatzaRutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA.
Bulent OzpolatDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
George A CalinDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Anil K SoodCenter for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Gabriel Lopez-BeresteinDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. Electronic address: glopez@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USRutgers, The State University of New Jersey · USHacettepe University · TR

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
UPR/MDACC Partnership for Excellence in Cancer Research(Parent Grant U54 CA096297)U54CA096297 · NCI · UNIVERSITY OF PUERTO RICO MED SCIENCES · PI Ilka C Rios · 2002 to 2026
$36.9M
UPR/MDACC Partnership for Excellence in Cancer Research (Luis Segarra supplement)U54CA096300 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Larkin Strong · 2002 to 2026
$23.8M
Novel extra cellular RNA-based combinatorial RNA inhibition therapyUH3TR000943 · NCATS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI CALIN, GEORGE A., LOPEZ-BERESTEIN, GABRIEL · 2015 to 2017
$3.2M
Protein-coding and non-coding RNA biomarkers for early detection of CLLR01CA182905 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI ABRUZZO, LYNNE V., CALIN, GEORGE A. · 2014 to 2018
$2.9M
miR-155 targeted therapeutics for precision medicine in lung cancerR01CA222007 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI CALIN, GEORGE A., CRISTINI, VITTORIO · 2018 to 2022
$2.6M
Viral miRs and cellular miRs in sepsisR01GM122775 · NIGMS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI CALIN, GEORGE A., LUPU, FLOREA · 2018 to 2020
$1.1M
A Pathway-based approach to investigate oncogenic mechanisms in ovarian cancerR00CA166228 · NCI · RBHS -CANCER INSTITUTE OF NEW JERSEY · PI GATZA, MICHAEL L · 2015 to 2017
$747k
A Pathway-based Approach to Investigate Oncogenic Mechanisms in Ovarian CancerK99CA166228 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI GATZA, MICHAEL L · 2013 to 2014
$200k
NCATS NIH HHS UH3 TR000943NCI NIH HHS K99 CA166228NCI NIH HHS P30 CA016672NCI NIH HHS R00 CA166228NCI NIH HHS R01 CA182905NCI NIH HHS R01 CA222007NCI NIH HHS U54 CA096297NCI NIH HHS U54 CA096300NIGMS NIH HHS R01 GM122775
6 · The paper itself

Abstract

backgroundCirculating miRNAs are known to play important roles in intercellular communication. However, the effects of exosomal miRNAs on cells are not fully understood.

methodsTo investigate the role of exosomal miR-1246 in ovarian cancer (OC) microenvironment, we performed RPPA as well as many other in vitro functional assays in ovarian cancer cells (sensitive; HeyA8, Skov3ip1, A2780 and chemoresistant; HeyA8-MDR, Skov3-TR, A2780-CP20). Therapeutic effect of miR-1246 inhibitor treatment was tested in OC animal model. We showed the effect of OC exosomal miR-1246 uptake on macrophages by co-culture experiments.

findingsSubstantial expression of oncogenic miR-1246 OC exosomes was found. We showed that Cav1 gene, which is the direct target of miR-1246, is involved in the process of exosomal transfer. A significantly worse overall prognosis were found for OC patients with high miR-1246 and low Cav1 expression based on TCGA data. miR-1246 expression were significantly higher in paclitaxel-resistant OC exosomes than in their sensitive counterparts. Overexpression of Cav1 and anti-miR-1246 treatment significantly sensitized OC cells to paclitaxel. We showed that Cav1 and multi drug resistance (MDR) gene is involved in the process of exosomal transfer. Our proteomic approach also revealed that miR-1246 inhibits Cav1 and acts through PDGFβ receptor at the recipient cells to inhibit cell proliferation. miR-1246 inhibitor treatment in combination with chemotherapy led to reduced tumor burden in vivo. Finally, we demonstrated that when OC cells are co-cultured with macrophages, they are capable of transferring their oncogenic miR-1246 to M2-type macrophages, but not M0-type macrophages.

interpretationOur results suggest that cancer exosomes may contribute to oncogenesis by manipulating neighboring infiltrating immune cells. This study provide a new mechanistic therapeutic approach to overcome chemoresistance and tumor progression through exosomal miR-1246 in OC patients.

Indexed as

ExosomesAnimalsApoptosisATP Binding Cassette Transporter, Subfamily BCaveolin 1Cell Line, TumorCell ProliferationDisease Models, AnimalDrug Resistance, NeoplasmFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMacrophagesMiceMicroRNAsATP Binding Cassette Transporter, Subfamily BCAV1 protein, humanCaveolin 1MicroRNAsReceptor, Platelet-Derived Growth Factor betaCav1ExosomemiR-1246oncomiROvarian cancerP-gp

Identifiers

PMID30487062
PMCPMC6306310
OpenAlexW2900760949

What OpenQuestion holds

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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.