Evidence map›Paper›PMID 31637848›Full record

ArticleMolecular oncology2020

miR-15a-5p, miR-15b-5p, and miR-16-5p inhibit tumor progression by directly targeting MYCN in neuroblastoma.

Srinivas Chava, C Patrick Reynolds, Anup S Pathania, Santhi Gorantla, Larisa Y Poluektova, Don W Coulter, Subash C Gupta, Manoj K Pandey, Kishore B Challagundla

Open access · goldAbstract read
In one paragraph

Article in Molecular oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed, 2 pooled it
15.7field-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

86 citing papers in PubMed, 2 syntheses or guidelines pooled it, 157 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Article
  5. Article
  6. Circulating microRNAs Expression as Prognosis Biomarker of Cholangiocarcinoma.Asian Pacific journal of cancer prevention : APJCP · 2026
    Article
  7. Article
  8. Review
  9. Article
  10. Apelin/APJ: Another Player in the Cancer Biology Network.International journal of molecular sciences · 2025
    Review
  11. Article
  12. FOXJ3, a novel tumor suppressor in neuroblastoma.Molecular therapy. Oncology · 2025
    Article
  13. Molecular regulation and therapeutic targeting ofFrontiers in cell and developmental biology · 2025
    Review
  14. Article
  15. Construction of aRenal failure · 2024
    Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

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

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 4 institutions in 2 countries.

Srinivas ChavaDepartment of Biochemistry and Molecular Biology & the Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
C Patrick ReynoldsChildhood Cancer Repository, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
Anup S PathaniaDepartment of Biochemistry and Molecular Biology & the Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
Santhi GorantlaDepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
Larisa Y PoluektovaDepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
Don W CoulterDepartment of Pediatrics, Division of Hematology/Oncology, University of Nebraska Medical Center, Omaha, NE, USA.
Subash C GuptaDepartment of Biochemistry, Institute of Science, Banaras Hindu University, Uttar Pradesh, India.
Manoj K PandeyDepartment of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA.
Kishore B ChallagundlaDepartment of Biochemistry and Molecular Biology & the Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.ORCID 0000-0001-8654-7717
University of Nebraska Medical Center · USBanaras Hindu University · INCooper Medical School of Rowan University · USTexas Tech University · US

Funding

Exosomic microRNAs and drug resistance in AML tumor microenvironmentK22CA197074 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI CHALLAGUNDLA, KISHORE B. · 2016 to 2018
$465k
NCI NIH HHS K22 CA197074
6 · The paper itself

Abstract

Neuroblastoma (NB) is the most common extracranial solid malignancy in children. Despite current aggressive treatment regimens, the prognosis for high-risk NB patients remains poor, with the survival of less than 40%. Amplification/stabilization of MYCN oncogene, in NB is associated with a high risk of recurrence. Thus, there is an urgent need for novel therapeutics. The deregulated expression of microRNA (miR) is reported in NB; nonetheless, its effect on MYCN regulation is poorly understood. First, we identified that miR-15a-5p, miR-15b-5p, and miR-16-5p (hereafter miR-15a, miR-15b or miR-16) were down-regulated in patient-derived xenografts (PDX) with high MYCN expression. MiR targeting sequences on MYCN mRNA were predicted using online databases such as TargetScan and miR database. The R2 database, containing 105 NB patients, showed an inverse correlation between MYCN mRNA and deleted in lymphocytic leukemia (DLEU) 2, a host gene of miR-15. Moreover, overexpression of miR-15a, miR-15b or miR-16 significantly reduced the levels of MYCN mRNA and N-Myc protein. Conversely, inhibiting miR dramatically enhanced MYCN mRNA and N-Myc protein levels, as well as increasing mRNA half-life in NB cells. By performing immunoprecipitation assays of argonaute-2 (Ago2), a core component of the RNA-induced silencing complex, we showed that miR-15a, miR-15b and miR-16 interact with MYCN mRNA. Luciferase reporter assays showed that miR-15a, miR-15b and miR-16 bind with 3'UTR of MYCN mRNA, resulting in MYCN suppression. Moreover, induced expression of miR-15a, miR-15b and miR-16 significantly reduced the proliferation, migration, and invasion of NB cells. Finally, transplanting miR-15a-, miR-15b- and miR-16-expressing NB cells into NSG mice repressed tumor formation and MYCN expression. These data suggest that miR-15a, miR-15b and miR-16 exert a tumor-suppressive function in NB by targeting MYCN. Therefore, these miRs could be considered as potential targets for NB treatment.

Indexed as

3' Untranslated RegionsAnimalsArgonaute ProteinsCell Line, TumorCell MovementCell SurvivalDatabases, GeneticDown-RegulationGene Expression Regulation, NeoplasticHeterograftsHumansMiceMice, Inbred NODMice, NudeMicroRNAsNeoplasm Invasiveness3' Untranslated RegionsAGO2 protein, humanArgonaute ProteinsDLEU2 lncRNA, humanMicroRNAsMIRN15 microRNA, humanMIRN16 microRNA, humanMYCN protein, humanN-Myc Proto-Oncogene ProteinRNA, Long NoncodingTransferasesAgo2microRNAMYCNneuroblastomapatient-derived xenografts

Identifiers

PMID31637848
PMCPMC6944109
OpenAlexW2981672224

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.