Evidence map›Paper›PMID 26472816›Full record

ArticleCirculation research2016

VEGF-Induced Expression of miR-17-92 Cluster in Endothelial Cells Is Mediated by ERK/ELK1 Activation and Regulates Angiogenesis.

Aránzazu Chamorro-Jorganes, Monica Y Lee, Elisa Araldi, Shira Landskroner-Eiger, Marta Fernández-Fuertes, Mahnaz Sahraei, Maria Quiles Del Rey, Coen van Solingen, Jun Yu, Carlos Fernández-Hernando and 2 more

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

Article in Circulation research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed
5.7field-weighted citation impact, top 3% 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

87 citing papers in PubMed, 169 citations in OpenAlex.

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  10. The alkylglycerone phosphate synthase sustains the resistance of gastric cancer cells to ferroptosis induced by Apatinib.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025
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  12. Biphasic regulation of miR-17∼92 transcription during hypoxia: roles of HIF1 and p53 hyperphosphorylation at ser15.American journal of physiology. Lung cellular and molecular physiology · 2024
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27 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 1 institution in 1 country.

Aránzazu Chamorro-JorganesFrom the Vascular Biology and Therapeutics Program (A.C.-J., M.Y.L., E.A., M.F.-F., M.S., J.Y., C.F.-H., W.C.S., Y.S.), Section of Comparative Medicine (A.C.-J., E.A., M.F.-F., M.S., M.Q.R., C.F.-H., Y.S.), Departments of Pathology (A.C.-J., E.A., M.F.-F., M.S., C.F.-H., Y.S.); Pharmacology (M.Y.L., S.L.-E., W.C.S.), and Internal Medicine, Section of Cardiovascular Medicine (J.Y.), Yale University School of Medicine, New Haven, CT; and Department of Medicine, New York University School of Medicine (C.S.).
Monica Y LeeFrom the Vascular Biology and Therapeutics Program (A.C.-J., M.Y.L., E.A., M.F.-F., M.S., J.Y., C.F.-H., W.C.S., Y.S.), Section of Comparative Medicine (A.C.-J., E.A., M.F.-F., M.S., M.Q.R., C.F.-H., Y.S.), Departments of Pathology (A.C.-J., E.A., M.F.-F., M.S., C.F.-H., Y.S.); Pharmacology (M.Y.L., S.L.-E., W.C.S.), and Internal Medicine, Section of Cardiovascular Medicine (J.Y.), Yale University School of Medicine, New Haven, CT; and Department of Medicine, New York University School of Medicine (C.S.).
Elisa AraldiFrom the Vascular Biology and Therapeutics Program (A.C.-J., M.Y.L., E.A., M.F.-F., M.S., J.Y., C.F.-H., W.C.S., Y.S.), Section of Comparative Medicine (A.C.-J., E.A., M.F.-F., M.S., M.Q.R., C.F.-H., Y.S.), Departments of Pathology (A.C.-J., E.A., M.F.-F., M.S., C.F.-H., Y.S.); Pharmacology (M.Y.L., S.L.-E., W.C.S.), and Internal Medicine, Section of Cardiovascular Medicine (J.Y.), Yale University School of Medicine, New Haven, CT; and Department of Medicine, New York University School of Medicine (C.S.).
Shira Landskroner-EigerFrom the Vascular Biology and Therapeutics Program (A.C.-J., M.Y.L., E.A., M.F.-F., M.S., J.Y., C.F.-H., W.C.S., Y.S.), Section of Comparative Medicine (A.C.-J., E.A., M.F.-F., M.S., M.Q.R., C.F.-H., Y.S.), Departments of Pathology (A.C.-J., E.A., M.F.-F., M.S., C.F.-H., Y.S.); Pharmacology (M.Y.L., S.L.-E., W.C.S.), and Internal Medicine, Section of Cardiovascular Medicine (J.Y.), Yale University School of Medicine, New Haven, CT; and Department of Medicine, New York University School of Medicine (C.S.).
Marta Fernández-FuertesFrom the Vascular Biology and Therapeutics Program (A.C.-J., M.Y.L., E.A., M.F.-F., M.S., J.Y., C.F.-H., W.C.S., Y.S.), Section of Comparative Medicine (A.C.-J., E.A., M.F.-F., M.S., M.Q.R., C.F.-H., Y.S.), Departments of Pathology (A.C.-J., E.A., M.F.-F., M.S., C.F.-H., Y.S.); Pharmacology (M.Y.L., S.L.-E., W.C.S.), and Internal Medicine, Section of Cardiovascular Medicine (J.Y.), Yale University School of Medicine, New Haven, CT; and Department of Medicine, New York University School of Medicine (C.S.).
Mahnaz SahraeiFrom the Vascular Biology and Therapeutics Program (A.C.-J., M.Y.L., E.A., M.F.-F., M.S., J.Y., C.F.-H., W.C.S., Y.S.), Section of Comparative Medicine (A.C.-J., E.A., M.F.-F., M.S., M.Q.R., C.F.-H., Y.S.), Departments of Pathology (A.C.-J., E.A., M.F.-F., M.S., C.F.-H., Y.S.); Pharmacology (M.Y.L., S.L.-E., W.C.S.), and Internal Medicine, Section of Cardiovascular Medicine (J.Y.), Yale University School of Medicine, New Haven, CT; and Department of Medicine, New York University School of Medicine (C.S.).
Maria Quiles Del ReyFrom the Vascular Biology and Therapeutics Program (A.C.-J., M.Y.L., E.A., M.F.-F., M.S., J.Y., C.F.-H., W.C.S., Y.S.), Section of Comparative Medicine (A.C.-J., E.A., M.F.-F., M.S., M.Q.R., C.F.-H., Y.S.), Departments of Pathology (A.C.-J., E.A., M.F.-F., M.S., C.F.-H., Y.S.); Pharmacology (M.Y.L., S.L.-E., W.C.S.), and Internal Medicine, Section of Cardiovascular Medicine (J.Y.), Yale University School of Medicine, New Haven, CT; and Department of Medicine, New York University School of Medicine (C.S.).
Coen van SolingenFrom the Vascular Biology and Therapeutics Program (A.C.-J., M.Y.L., E.A., M.F.-F., M.S., J.Y., C.F.-H., W.C.S., Y.S.), Section of Comparative Medicine (A.C.-J., E.A., M.F.-F., M.S., M.Q.R., C.F.-H., Y.S.), Departments of Pathology (A.C.-J., E.A., M.F.-F., M.S., C.F.-H., Y.S.); Pharmacology (M.Y.L., S.L.-E., W.C.S.), and Internal Medicine, Section of Cardiovascular Medicine (J.Y.), Yale University School of Medicine, New Haven, CT; and Department of Medicine, New York University School of Medicine (C.S.).
Jun YuFrom the Vascular Biology and Therapeutics Program (A.C.-J., M.Y.L., E.A., M.F.-F., M.S., J.Y., C.F.-H., W.C.S., Y.S.), Section of Comparative Medicine (A.C.-J., E.A., M.F.-F., M.S., M.Q.R., C.F.-H., Y.S.), Departments of Pathology (A.C.-J., E.A., M.F.-F., M.S., C.F.-H., Y.S.); Pharmacology (M.Y.L., S.L.-E., W.C.S.), and Internal Medicine, Section of Cardiovascular Medicine (J.Y.), Yale University School of Medicine, New Haven, CT; and Department of Medicine, New York University School of Medicine (C.S.).
Carlos Fernández-HernandoFrom the Vascular Biology and Therapeutics Program (A.C.-J., M.Y.L., E.A., M.F.-F., M.S., J.Y., C.F.-H., W.C.S., Y.S.), Section of Comparative Medicine (A.C.-J., E.A., M.F.-F., M.S., M.Q.R., C.F.-H., Y.S.), Departments of Pathology (A.C.-J., E.A., M.F.-F., M.S., C.F.-H., Y.S.); Pharmacology (M.Y.L., S.L.-E., W.C.S.), and Internal Medicine, Section of Cardiovascular Medicine (J.Y.), Yale University School of Medicine, New Haven, CT; and Department of Medicine, New York University School of Medicine (C.S.).
William C SessaFrom the Vascular Biology and Therapeutics Program (A.C.-J., M.Y.L., E.A., M.F.-F., M.S., J.Y., C.F.-H., W.C.S., Y.S.), Section of Comparative Medicine (A.C.-J., E.A., M.F.-F., M.S., M.Q.R., C.F.-H., Y.S.), Departments of Pathology (A.C.-J., E.A., M.F.-F., M.S., C.F.-H., Y.S.); Pharmacology (M.Y.L., S.L.-E., W.C.S.), and Internal Medicine, Section of Cardiovascular Medicine (J.Y.), Yale University School of Medicine, New Haven, CT; and Department of Medicine, New York University School of Medicine (C.S.).
Yajaira SuárezFrom the Vascular Biology and Therapeutics Program (A.C.-J., M.Y.L., E.A., M.F.-F., M.S., J.Y., C.F.-H., W.C.S., Y.S.), Section of Comparative Medicine (A.C.-J., E.A., M.F.-F., M.S., M.Q.R., C.F.-H., Y.S.), Departments of Pathology (A.C.-J., E.A., M.F.-F., M.S., C.F.-H., Y.S.); Pharmacology (M.Y.L., S.L.-E., W.C.S.), and Internal Medicine, Section of Cardiovascular Medicine (J.Y.), Yale University School of Medicine, New Haven, CT; and Department of Medicine, New York University School of Medicine (C.S.). yajaira.suarez@yale.edu.
Yale University · US

Funding

Yale Pathology Tissue Services Shared ResourceP30CA016359 · NCI · YALE UNIVERSITY · PI DAVID L RIMM · 1985 to 2026
$85.0M
PHOSPHORYLATION AND ENDOTHELIAL NITRIC OXIDE PRODUCTIONR01HL064793 · NHLBI · YALE UNIVERSITY · PI SESSA, WILLIAM C · 2000 to 2016
$6.3M
Endothelial NOS by protein to protein interactionsR37HL061371 · NHLBI · YALE UNIVERSITY · PI SESSA, WILLIAM C · 2009 to 2017
$4.1M
microRNAs in vascular diseasesR01HL105945 · NHLBI · YALE UNIVERSITY · PI SUAREZ, YAJAIRA · 2011 to 2020
$3.7M
Endothelial NOS by Protein-Protein IntractionsR01HL061371 · NHLBI · YALE UNIVERSITY · PI SESSA, WILLIAM C · 1999 to 2008
$3.6M
Caveolin-1 in Lipoprotein Metabolism and Atherosclerosis.R01HL106063 · NHLBI · YALE UNIVERSITY · PI FERNANDEZ HERNANDO, CARLOS · 2011 to 2016
$2.5M
Role of microRNAs in lipid metabolism and cardiovascular diseaseR01HL107953 · NHLBI · YALE UNIVERSITY · PI FERNANDEZ HERNANDO, CARLOS · 2011 to 2016
$2.4M
ER-associated protein Reticulon in atherosclerosisR01HL126933 · NHLBI · YALE UNIVERSITY · PI YU, JUN · 2015 to 2018
$1.6M
NCI NIH HHS P30 CA016359NHLBI NIH HHS P01 HL1070295NHLBI NIH HHS R01 HL105945NHLBI NIH HHS R01 HL106063NHLBI NIH HHS R01 HL107953NHLBI NIH HHS R01 HL126933NHLBI NIH HHS R01 HL61371NHLBI NIH HHS R01 HL64793NHLBI NIH HHS R37 HL061371
6 · The paper itself

Abstract

rationaleSeveral lines of evidence indicate that the regulation of microRNA (miRNA) levels by different stimuli may contribute to the modulation of stimulus-induced responses. The miR-17-92 cluster has been linked to tumor development and angiogenesis, but its role in vascular endothelial growth factor-induced endothelial cell (EC) functions is unclear and its regulation is unknown.

objectiveThe purpose of this study was to elucidate the mechanism by which VEGF regulates the expression of miR-17-92 cluster in ECs and determine its contribution to the regulation of endothelial angiogenic functions, both in vitro and in vivo. This was done by analyzing the effect of postnatal inactivation of miR-17-92 cluster in the endothelium (miR-17-92 iEC-KO mice) on developmental retinal angiogenesis, VEGF-induced ear angiogenesis, and tumor angiogenesis. METHODS AND

resultsHere, we show that Erk/Elk1 activation on VEGF stimulation of ECs is responsible for Elk-1-mediated transcription activation (chromatin immunoprecipitation analysis) of the miR-17-92 cluster. Furthermore, we demonstrate that VEGF-mediated upregulation of the miR-17-92 cluster in vitro is necessary for EC proliferation and angiogenic sprouting. Finally, we provide genetic evidence that miR-17-92 iEC-KO mice have blunted physiological retinal angiogenesis during development and diminished VEGF-induced ear angiogenesis and tumor angiogenesis. Computational analysis and rescue experiments show that PTEN (phosphatase and tensin homolog) is a target of the miR-17-92 cluster and is a crucial mediator of miR-17-92-induced EC proliferation. However, the angiogenic transcriptional program is reduced when miR-17-92 is inhibited.

conclusionsTaken together, our results indicate that VEGF-induced miR-17-92 cluster expression contributes to the angiogenic switch of ECs and participates in the regulation of angiogenesis.

Indexed as

AnimalsCell ProliferationEndothelium, VascularGene Expression RegulationHumansHuman Umbilical Vein Endothelial CellsMAP Kinase Signaling SystemMiceMice, KnockoutMicroRNAsNeovascularization, PhysiologicVascular Endothelial Growth Factor AMicroRNAsMIRN17-92 microRNA, mouseVascular Endothelial Growth Factor Avascular endothelial growth factor A, mousecell proliferationendothelial cellsmicroRNAstranscription activationvascular endothelial growth factor A

Identifiers

PMID26472816
PMCPMC4703066
OpenAlexW2175574776

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