Evidence map›Paper›PMID 26915294›Full record

ArticleCell death and differentiation2016

Histone deacetylase inhibition reveals a tumor-suppressive function of MYC-regulated miRNA in breast and lung carcinoma.

C M Adams, C M Eischen

Open access · bronzeAbstract read
In one paragraph

Article in Cell death and differentiation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

17 citing papers in PubMed, 30 citations in OpenAlex.

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  11. Review
  12. The Roles of Histone Deacetylases and Their Inhibitors in Cancer Therapy.Frontiers in cell and developmental biology · 2020
    Review
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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

2 authors at 1 institution in 1 country.

C M AdamsDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
C M EischenDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Vanderbilt University Medical Center · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
X-Ray Crystallography and Macromolecular CharacterizationP30CA056036 · NCI · THOMAS JEFFERSON UNIVERSITY · PI DANIEL P SILVER · 1995 to 2026
$94.8M
Novel mechanisms of oncogenic transformation in lung cancerR01CA177786 · NCI · VANDERBILT UNIVERSITY · PI EISCHEN, CHRISTINE M. · 2014 to 2018
$1.6M
Novel Mechanism for Myc-Induced ApoptosisF31CA165728 · NCI · VANDERBILT UNIVERSITY · PI ADAMS, CLARE MARIE · 2012 to 2014
$80k
NCI NIH HHS F31 CA165728NCI NIH HHS P30 CA056036NCI NIH HHS P30 CA068485NCI NIH HHS R01 CA177786
6 · The paper itself

Abstract

Histone deacetylase (HDAC) inhibition leads to dynamic changes in the epigenetic landscape that is postulated to alter the expression of critical mediators of cellular proliferation and death. While current HDAC inhibitors have shown to be efficacious in the treatment of specific hematologic malignancies, their therapeutic utility in epithelial-based cancers warrants further evaluation. Moreover, the mechanisms of HDAC inhibition-induced cancer cell death are not completely understood. Therefore, elucidation of the underlying pathways engaged by HDAC inhibition may enable the development of more effective therapeutic strategies. Here, we report that HDAC inhibition in human breast and lung carcinoma cells activates an apoptotic mechanism mediated by microRNA (miRNA) and induced by the oncogene MYC. Specifically, following HDAC inhibition, MYC, which normally represses miR-15 and let-7 families, transcriptionally activated their expression and MYC was required for this miRNA upregulation. As a result, transcript levels of the tumor-suppressive miR-15 and let-7 families increased, which targeted and decreased the expression of the crucial prosurvival genes BCL-2 and BCL-XL, respectively. MYC was also required for the downregulation of BCL-2 and BCL-XL following HDAC inhibition. Blocking the binding sites of the miR-15 and let-7 families in the 3'-untranslated regions of BCL-2 and BCL-XL protected against HDAC inhibition-induced apoptosis. These results provide important insight into the molecular underpinnings of HDAC inhibition-induced cell death in breast and lung cancer and reveal a tumor-suppressive role for MYC-regulated miRNA that is activated with HDAC inhibition.

Indexed as

3' Untranslated RegionsA549 CellsApoptosisBase Sequencebcl-X ProteinBinding SitesBreast NeoplasmsCell Line, TumorChromatin ImmunoprecipitationFemaleHistone Deacetylase InhibitorsHumansLung NeoplasmsMicroRNAsProto-Oncogene Proteins c-bcl-2Proto-Oncogene Proteins c-myc3' Untranslated Regionsbcl-X ProteinHistone Deacetylase InhibitorsMicroRNAsProto-Oncogene Proteins c-bcl-2Proto-Oncogene Proteins c-myc

Identifiers

PMID26915294
PMCPMC4947678
OpenAlexW2275472821

What OpenQuestion holds

Textmetadata
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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.