Evidence map›Paper›PMID 21809359›Full record

ArticleHepatology (Baltimore, Md.)2011

MicroRNA down-regulated in human cholangiocarcinoma control cell cycle through multiple targets involved in the G1/S checkpoint.

Alexandru V Olaru, Gabriel Ghiaur, Sumitaka Yamanaka, Delgermaa Luvsanjav, Fangmei An, Irinel Popescu, Sorin Alexandrescu, Sarah Allen, Timothy M Pawlik, Michael Torbenson and 8 more

Open access · bronzeAbstract read
In one paragraph

Article in Hepatology (Baltimore, Md.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 2 pooled it
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

62 citing papers in PubMed, 2 syntheses or guidelines pooled it, 98 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. In Vivo Models for Cholangiocarcinoma-What Can We Learn for Human Disease?International journal of molecular sciences · 2020
    Review
  9. Review
  10. Article
  11. Inhibition of histone deacetylase 3 by MiR-494 alleviates neuronal loss and improves neurological recovery in experimental stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019
    Article
  12. Article
  13. Animal models of cholangiocarcinoma.Biochimica et biophysica acta. Molecular basis of disease · 2019
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

2 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

18 authors at 5 institutions in 3 countries.

Alexandru V OlaruDivision of Gastroenterology and Hepatology, Johns Hopkins Hospital, Baltimore, MD 21205, USA.
Gabriel Ghiaur
Sumitaka Yamanaka
Delgermaa Luvsanjav
Fangmei An
Irinel Popescu
Sorin Alexandrescu
Sarah Allen
Timothy M Pawlik
Michael Torbenson
Christos Georgiades
Lewis R Roberts
Gregory J Gores
Anne Ferguson-Smith
Maria I Almeida
George A Calin
Esteban Mezey
Florin M Selaru
Johns Hopkins Hospital · USInstitutul Clinic Fundeni · ROMayo Clinic in Arizona · USThe University of Texas MD Anderson Cancer Center · USUniversity of Cambridge · GB

Funding

MicroRNA involvement in the regulation of biliary epitheliumK08DK090154 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI SELARU, FLORIN · 2011 to 2015
$706k
NIDDK NIH HHS DK090154-01NIDDK NIH HHS K08 DK090154
6 · The paper itself

Abstract

unlabelledMicroRNAs (miRs) recently emerged as prominent regulators of cancer processes. In the current study we aimed at elucidating regulatory pathways and mechanisms through which miR-494, one of the miR species found to be down-regulated in cholangiocarcinoma (CCA), participates in cancer homeostasis. miR-494 was identified as down-regulated in CCA based on miR arrays. Its expression was verified with quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR). To enforce miR expression, we employed both transfection methods, as well as a retroviral construct to stably overexpress miR-494. Up-regulation of miR-494 in cancer cells decreased growth, consistent with a functional role. mRNA arrays of cells treated with miR-494, followed by pathway analysis, suggested that miR-494 impacts cell cycle regulation. Cell cycle analyses demonstrated that miR-494 induces a significant G1/S checkpoint reinforcement. Further analyses demonstrated that miR-494 down-regulates multiple molecules involved in this transition checkpoint. Luciferase reporter assays demonstrated a direct interaction between miR-494 and the 3'-untranslated region of cyclin-dependent kinase 6 (CDK6). Last, xenograft experiments demonstrated that miR-494 induces a significant cancer growth retardation in vivo.

conclusionOur findings demonstrate that miR-494 is down-regulated in CCA and that its up-regulation induces cancer cell growth retardation through multiple targets involved in the G1-S transition. These findings support the paradigm that miRs are salient cellular signaling pathway modulators, and thus represent attractive therapeutic targets. miR-494 emerges as an important regulator of CCA growth and its further study may lead to the development of novel therapeutics.

Indexed as

AnimalsBile Duct NeoplasmsBile Ducts, IntrahepaticCell Cycle CheckpointsCholangiocarcinomaCyclin-Dependent Kinase 6Down-RegulationGene Expression ProfilingHumansMiceMice, Inbred NODMicroRNAsNeoplasm TransplantationTransfectionTransplantation, HeterologousCyclin-Dependent Kinase 6MicroRNAsMIRN494 microRNA, human

Identifiers

PMID21809359
PMCPMC3212606
OpenAlexW2086460125

What OpenQuestion holds

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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.