Evidence map›Paper›PMID 22180294›Full record

ArticleEMBO molecular medicine2012

Concerted functions of HDAC1 and microRNA-574-5p repress alternatively spliced ceramide synthase 1 expression in human cancer cells.

Marisa Meyers-Needham, Suriyan Ponnusamy, Salih Gencer, Wenhui Jiang, Raquela J Thomas, Can E Senkal, Besim Ogretmen

Open access · goldAbstract read
In one paragraph

Article in EMBO molecular medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

37 citing papers in PubMed, 70 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. miR-574-5p in epigenetic regulation and Toll-like receptor signaling.Cell communication and signaling : CCS · 2024
    Review
  7. Review
  8. Opportunistic pathogeniScience · 2024
    Article
  9. Article
  10. Review
  11. Review
  12. Characterization of Lipid Alterations by OncogenicOmics : a journal of integrative biology · 2023
    Article
  13. Review
  14. Review
  15. Article
  16. Review
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  18. 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

7 authors at 3 institutions in 1 country.

Marisa Meyers-NeedhamDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, SC, USA.
Suriyan Ponnusamy
Salih Gencer
Wenhui Jiang
Raquela J Thomas
Can E Senkal
Besim Ogretmen
Medical University of South Carolina · USUniversity of South Carolina · USMUSC Hollings Cancer Center · US

Funding

Sphingolipids in Cancer Therapy and AngiogenesisP01CA097132 · NCI · STATE UNIVERSITY NEW YORK STONY BROOK · PI YUSUF AWNI HANNUN · 2003 to 2026
$30.8M
SOUTH CAROLINA CLINICAL & TRANSLATIONAL RESEARCH INSTITUTE (SCTR)UL1RR029882 · NCRR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI BRADY, KATHLEEN T. · 2009 to 2011
$10.1M
South Carolina Clinical & Translational Research Institute (SCTR)UL1TR000062 · NCATS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI BRADY, KATHLEEN T. · 2012 to 2014
$9.4M
Ceramide Signaling in the Regulation of Head & Neck Cancer Cell Death and TherapyR01DE016572 · NIDCR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI OGRETMEN, BESIM · 2005 to 2025
$7.4M
MUSC Minority Student Development ProgramR25GM072643 · NIGMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI ERGUL, ADVIYE, RINKER, JENNIFER ANNE · 2005 to 2023
$5.8M
Regulation of Telomerase by Sphingolipid Signaling in Lung CancerR01CA088932 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI OGRETMEN, BESIM · 2002 to 2017
$3.3M
MUSC FACIL EXPANSION &RENOV: SLE C06RR015455 · NCRR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI RAYMOND, JOHN R · 2002 to 2002
$2.0M
NCATS NIH HHS UL1 TR000062NCI NIH HHS CA088932NCI NIH HHS CA097132NCI NIH HHS P01 CA097132NCI NIH HHS R01 CA088932NCRR NIH HHS C06 RR015455NCRR NIH HHS C06RR015455NCRR NIH HHS UL1 RR029882NIDCR NIH HHS DE016572NIDCR NIH HHS R01 DE016572NIGMS NIH HHS R25 GM072643
6 · The paper itself

Abstract

Histone deacetylases (HDACs) and microRNAs (miRs) have pro-survival roles, but the mechanism behind this is unclear. Repression of ceramide synthase 1 (CerS1), altering C(18) -ceramide generation, was linked to drug resistance and metastasis. Here we report that the CerS1 promoter was repressed by HDAC1-dependent inhibition of Sp1 recruitment to two specific GC-boxes spanning the -177 and -139 region. Moreover, an alternatively spliced variant CerS1 mRNA (CerS1-2) was detected mainly in cancer cells or primary tumour tissues compared to controls, which was targeted by miR-574-5p for degradation. A specific 3'UTR-targeting site, localized within the retained intron between exons 6 and 7, was identified, and its mutation, or miR-574-5p knockdown prevented the degradation of CerS1-2 mRNA. Interference with HDAC1 and miR-574-5p reconstituted CerS1-2 expression and C(18) -ceramide generation in multiple human cancer cell lines, which subsequently inhibited proliferation and anchorage-independent growth. Accordingly, knockdown of CerS1 partially protected cancer cells from MS-275/miR-574-5p siRNA-mediated growth inhibition. Thus, these data suggest that the HDAC1/miR-574-5p axis might provide a novel therapeutic target to reconstitute tumour suppressor CerS1/ceramide signalling.

Indexed as

Gene Expression Regulation, Neoplastic3' Untranslated RegionsAlternative SplicingCell Line, TumorCell ProliferationHistone Deacetylase 1HumansMembrane ProteinsMicroRNAsNeoplasmsSignal TransductionSphingosine N-AcyltransferaseTumor Suppressor Proteins3' Untranslated RegionsCERS1 protein, humanCERS2 protein, humanHDAC1 protein, humanHistone Deacetylase 1Membrane ProteinsMicroRNAsMIRN574 microRNA, humanSphingosine N-AcyltransferaseTumor Suppressor Proteins

Identifiers

PMID22180294
PMCPMC3376837
OpenAlexW2165197006

What OpenQuestion 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 OpenQuestion graph.