Evidence map›Paper›PMID 21418558›Full record

ArticleMolecular cancer2011

miR-449 inhibits cell proliferation and is down-regulated in gastric cancer.

Tony Bou Kheir, Ewa Futoma-Kazmierczak, Anders Jacobsen, Anders Krogh, Linda Bardram, Christoffer Hother, Kirsten Grønbæk, Birgitte Federspiel, Anders H Lund, Lennart Friis-Hansen

Open access · goldAbstract read
In one paragraph

Article in Molecular cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
133citing papers in PubMed, 1 pooled it
8.7field-weighted citation impact, top 2% 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

133 citing papers in PubMed, 1 synthesis or guideline pooled it, 243 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. How MicroRNAs Command the Battle against Cancer.International journal of molecular sciences · 2024
    Review
  11. MiR-449a antagonizes EMT through IL-6-mediatedMolecular therapy. Nucleic acids · 2024
    Article
  12. Review
  13. Article
  14. The regulation roles of miRNAs in Helicobacter pylori infection.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
    Review
  15. Review
  16. Signaling pathways and therapeutic interventions in gastric cancer.Signal transduction and targeted therapy · 2022
    Review
  17. Article
  18. Article
  19. Article
  20. Article

73 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

10 authors at 2 institutions in 1 country.

Tony Bou KheirBRIC-Biotech Research & Innovation Centre and Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark.
Ewa Futoma-Kazmierczak
Anders Jacobsen
Anders Krogh
Linda Bardram
Christoffer Hother
Kirsten Grønbæk
Birgitte Federspiel
Anders H Lund
Lennart Friis-Hansen
University of Copenhagen · DKRigshospitalet · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGastric cancer is the fourth most common cancer in the world and the second most prevalent cause of cancer related death. The development of gastric cancer is mainly associated with H. Pylori infection leading to a focus in pathology studies on bacterial and environmental factors, and to a lesser extent on the mechanistic development of the tumour. MicroRNAs are small non-coding RNA molecules involved in post-transcriptional gene regulation. They are found to regulate genes involved in diverse biological functions and alterations in microRNA expression have been linked to the pathogenesis of many malignancies. The current study is focused on identifying microRNAs involved in gastric carcinogenesis and to explore their mechanistic relevance by characterizing their targets.

resultsInvitrogen NCode miRNA microarrays identified miR-449 to be decreased in 1-year-old Gastrin KO mice and in H. Pylori infected gastric tissues compared to tissues from wild type animals. Growth rate of gastric cell lines over-expressing miR-449 was inhibited by 60% compared to controls. FACS cell cycle analysis of miR-449 over-expressing cells showed a significant increase in the sub-G1 fraction indicative of apoptosis. ß-Gal assays indicated a senescent phenotype of gastric cell lines over-expressing miR-449. Affymetrix 133v2 arrays identified GMNN, MET, CCNE2, SIRT1 and CDK6 as miR-449 targets. Luciferase assays were used to confirm GMNN, MET, CCNE2 and SIRT1 as direct targets. We also show that miR-449 over-expression activated p53 and its downstream target p21 as well as the apoptosis markers cleaved CASP3 and PARP. Importantly, qPCR analyses showed a loss of miR-449 expression in human clinical gastric tumours compared to normal tissues.

conclusionsIn this study, we document a diminished expression of miR-449 in Gastrin KO mice and further confirmed its loss in human gastric tumours. We investigated the function of miR-449 by identifying its direct targets. Furthermore we show that miR-449 induces senescence and apoptosis by activating the p53 pathway.

Indexed as

Gene Expression Regulation, NeoplasticAdenomaAnimalsBase SequenceCell CycleCell Line, TumorCell ProliferationCellular SenescenceDown-RegulationGastrinsHelicobacter InfectionsHelicobacter pyloriHumansMiceMice, KnockoutMicroRNAsGastrinsMicroRNAsMIRN34 microRNA, humanMIRN449 microRNA, humanMirn449 microRNA, mouseTumor Suppressor Protein p53

Identifiers

PMID21418558
PMCPMC3070685
OpenAlexW2123356446

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.