Evidence map›Paper›PMID 21768308›Full record

ArticleMolecular and cellular biology2011

Translational control of TOP2A influences doxorubicin efficacy.

Subramanya Srikantan, Kotb Abdelmohsen, Eun Kyung Lee, Kumiko Tominaga, Sarah S Subaran, Yuki Kuwano, Ritu Kulshrestha, Rohit Panchakshari, Hyeon Ho Kim, Xiaoling Yang and 7 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular and cellular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
4.7field-weighted citation impact, top 4% 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

66 citing papers in PubMed, 95 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. RNA binding proteins in cancer chemotherapeutic drug resistance.Frontiers in cell and developmental biology · 2024
    Review
  7. Article
  8. Article
  9. Relationship between HuR and tumor drug resistance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
    Review
  10. Article
  11. Review
  12. Effects of hsa-miR-9-3p and hsa-miR-9-5p on Topoisomerase IIThe Journal of pharmacology and experimental therapeutics · 2023
    Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Human antigen R and drug resistance in tumors.Investigational new drugs · 2019
    Review
  19. Review
  20. Article

6 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

17 authors at 3 institutions in 2 countries.

Subramanya SrikantanLaboratory of Molecular Biology and Immunology, NIA-IRP, NIH, Baltimore, Maryland 21224, USA.
Kotb Abdelmohsen
Eun Kyung Lee
Kumiko Tominaga
Sarah S Subaran
Yuki Kuwano
Ritu Kulshrestha
Rohit Panchakshari
Hyeon Ho Kim
Xiaoling Yang
Jennifer L Martindale
Bernard S Marasa
Mihee M Kim
Robert P Wersto
Fred E Indig
Dipanjan Chowdhury
Myriam Gorospe
Dana-Farber Cancer Institute · USHarvard University · USSamsung (South Korea) · KR

Funding

Post-transcriptional Regulation Of Proliferative and Stress Response GenesZIAAG000511 · NIA · NATIONAL INSTITUTE ON AGING · PI GOROSPE, MYRIAM · 2009 to 2025
$25.4M
NIA/RRB Confocal Imaging FacilityZICAG000615 · NIA · NATIONAL INSTITUTE ON AGING · PI INDIG, FRED · 2009 to 2025
$17.9M
Flow Cytometry Laboratory (Scientific Core)ZICAG000618 · NIA · NATIONAL INSTITUTE ON AGING · PI WENG, NAN-PING PETER · 2009 to 2025
$9.5M
Molecular mechanism and relevance of microRNAs in DSB repair pathway choiceR01CA142698 · NCI · DANA-FARBER CANCER INST · PI CHOWDHURY, DIPANJAN · 2010 to 2019
$3.8M
NCI NIH HHS R01 CA142698NCI NIH HHS R01CA142698
6 · The paper itself

Abstract

The cellular abundance of topoisomerase IIα (TOP2A) critically maintains DNA topology after replication and determines the efficacy of TOP2 inhibitors in chemotherapy. Here, we report that the RNA-binding protein HuR, commonly overexpressed in cancers, binds to the TOP2A 3'-untranslated region (3'UTR) and increases TOP2A translation. Reducing HuR levels triggered the recruitment of TOP2A transcripts to RNA-induced silencing complex (RISC) components and to cytoplasmic processing bodies. Using a novel MS2-tagged RNA precipitation method, we identified microRNA miR-548c-3p as a mediator of these effects and further uncovered that the interaction of miR-548c-3p with the TOP2A 3'UTR repressed TOP2A translation by antagonizing the action of HuR. Lowering TOP2A by silencing HuR or by overexpressing miR-548c-3p selectively decreased DNA damage after treatment with the chemotherapeutic agent doxorubicin. In sum, HuR enhances TOP2A translation by competing with miR-548c-3p; their combined actions control TOP2A expression levels and determine the effectiveness of doxorubicin.

Indexed as

3' Untranslated RegionsAntibiotics, AntineoplasticAntigens, NeoplasmAntigens, SurfaceDNADNA-Binding ProteinsDNA DamageDNA Topoisomerases, Type IIDoxorubicinELAV-Like Protein 1ELAV ProteinsGene Expression RegulationHeLa CellsHumansMicroRNAsPoly-ADP-Ribose Binding Proteins3' Untranslated RegionsAntibiotics, AntineoplasticAntigens, NeoplasmAntigens, SurfaceDNADNA-Binding ProteinsDNA Topoisomerases, Type IIDoxorubicinELAVL1 protein, humanELAV-Like Protein 1ELAV ProteinsMicroRNAsMIRN548 microRNA, humanPoly-ADP-Ribose Binding ProteinsRNA-Binding ProteinsRNA-Induced Silencing ComplexRNA, MessengerRNA, Small InterferingTOP2A protein, human

Identifiers

PMID21768308
PMCPMC3165726
OpenAlexW2156205933

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.