Evidence map›Paper›PMID 26045293›Full record

Trial reportHaematologica2015

Differential hypoxic regulation of the microRNA-146a/CXCR4 pathway in normal and leukemic monocytic cells: impact on response to chemotherapy.

Isabella Spinello, Maria Teresa Quaranta, Rosa Paolillo, Elvira Pelosi, Anna Maria Cerio, Ernestina Saulle, Francesco Lo Coco, Ugo Testa, Catherine Labbaye

Open access · goldAbstract readClinical Trial
In one paragraph

Trial report in Haematologica, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
0.6field-weighted citation impact, top 33% 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

16 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
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  9. The hypoxia-induced changes in miRNA-mRNA in RNA-induced silencing complexes and HIF-2 induced miRNAs in human endothelial cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022
    Article
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  16. Inhibition of atherogenesis by the COP9 signalosome subunit 5 in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
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

9 authors at 1 institution in 1 country.

Isabella SpinelloDepartment of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, University of Rome "Tor Vergata", Rome, Italy.
Maria Teresa QuarantaDepartment of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, University of Rome "Tor Vergata", Rome, Italy.
Rosa PaolilloDepartment of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, University of Rome "Tor Vergata", Rome, Italy.
Elvira PelosiDepartment of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, University of Rome "Tor Vergata", Rome, Italy.
Anna Maria CerioDepartment of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, University of Rome "Tor Vergata", Rome, Italy.
Ernestina SaulleDepartment of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, University of Rome "Tor Vergata", Rome, Italy.
Francesco Lo CocoDepartment of Biomedicine and Prevention, University of Rome "Tor Vergata", Rome, Italy Fondazione Santa Lucia, Rome, Italy.
Ugo TestaDepartment of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, University of Rome "Tor Vergata", Rome, Italy.
Catherine LabbayeDepartment of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, University of Rome "Tor Vergata", Rome, Italy catherine.labbaye@iss.it.
University of Rome Tor Vergata · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

High expression of the chemokine receptor 4, CXCR4, associated with a negative prognosis in acute myeloid leukemia, is related to hypoxia. Because CXCR4 expression is under the post-transcriptional control of microRNA-146a in normal and leukemic monocytic cells, we first investigated the impact of hypoxia on microRNA-146a and CXCR4 expression during monocytopoiesis and in acute monocytic leukemia. We then analyzed the effects of hypoxia on drug sensitivity of CXCR4-expressing leukemic cells. We found that microRNA-146a is a target of hypoxia-inducible factor-1α or -2α in relation to the stage of monocytopoiesis and the level of hypoxia, and demonstrated the regulation of the microRNA-146a/CXCR4 pathway by hypoxia in monocytes derived from CD34(+) cells. Thus, in myeloid leukemic cell lines, hypoxia-mediated control of the microRNA-146a/CXCR4 pathway depends only on the capacity of hypoxia-inducible factor-1α to up-regulate microRNA-146a, which in turn decreases CXCR4 expression. However, at variance with normal monocytic cells and leukemic cell lines, in acute monocytic leukemia overexpressing CXCR4, hypoxia up-modulates microRNA-146a but fails to down-modulate CXCR4 expression. We then investigated the effect of hypoxia on the response of leukemic cells to chemotherapy alone or in combination with stromal-derived factor-1α. We found that hypoxia increases stromal-derived factor-1α-induced survival of leukemic cells by decreasing their sensitivity to anti-leukemic drugs. Altogether, our results demonstrate that hypoxia-mediated regulation of microRNA-146a, which controls CXCR4 expression in monocytic cells, is lost in acute monocytic leukemia, thus contributing to maintaining CXCR4 overexpression and protecting the cells from anti-leukemic drugs in the hypoxic bone marrow microenvironment.

Indexed as

Leukemia, Monocytic, AcuteBasic Helix-Loop-Helix ProteinsCell HypoxiaEndothelial PAS Domain-Containing Protein 1FemaleGene Expression Regulation, LeukemicHumansHypoxia-Inducible Factor 1, alpha SubunitMaleMicroRNAsMonocytesNeoplasm ProteinsReceptors, CXCR4RNA, NeoplasmU937 CellsBasic Helix-Loop-Helix ProteinsCXCR4 protein, humanEndothelial PAS Domain-Containing Protein 1HIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitMicroRNAsMIRN146 microRNA, humanNeoplasm ProteinsReceptors, CXCR4RNA, Neoplasm

Identifiers

PMID26045293
PMCPMC4800689
OpenAlexW2123267899

What Socratic 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 Socratic graph.