Evidence map›Paper›PMID 33582945›Full record

ArticleMolecular and cellular biochemistry2021

Twist activates miR-22 to suppress estrogen receptor alpha in breast cancer.

Farhad Vesuna, Ala Lisok, Paul van Diest, Venu Raman

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biochemistry, 2021. 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
1.5field-weighted citation impact, top 20% 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, 22 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. The Role of the Fox Gene in Breast Cancer Progression.International journal of molecular sciences · 2025
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. miR-22 gene therapy treats HCC by promoting anti-tumor immunity and enhancing metabolism.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. DNMT3A and DNMT3B in Breast Tumorigenesis and Potential Therapy.Frontiers in cell and developmental biology · 2022
    Review
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

4 authors at 2 institutions in 2 countries.

Farhad VesunaDepartment of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. fvesuna1@jhmi.edu.ORCID http://orcid.org/0000-0002-0356-5096
Ala LisokDepartment of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Paul van DiestDepartment of Pathology, University of Utrecht, Utrecht, The Netherlands.
Venu RamanDepartment of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. vraman2@jhmi.edu.ORCID http://orcid.org/0000-0003-2322-1423
Johns Hopkins University · USUtrecht University · NL

Funding

The Role of HOXA5 in Breast CancerR01CA097226 · NCI · JOHNS HOPKINS UNIVERSITY · PI RAMAN, VENU · 2004 to 2008
$1.5M
Maryland Stem Cell Research Fund MDTSCRC0064Maryland Stem Cell Research Fund MDTSCRC0072NCI NIH HHS R01 CA097226NCI NIH HHS R01CA097226
6 · The paper itself

Abstract

TWIST1 (Twist) is a basic helix-loop-helix transcription factor that is overexpressed in many cancers and promotes tumor cell invasion, metastasis, and recurrence. In this study, we demonstrate that Twist upregulates expression of microRNA 22 (miR-22) which, in turn, downregulates estrogen receptor alpha (ER) expression in breast cancer. Initial analysis of miR-22 and Twist expression in a panel of breast cancer cell lines showed a direct correlation between Twist and miR-22 levels with miR-22 being highly expressed in ER negative cell lines. Overexpressing Twist caused increased miR-22 levels while downregulating it led to decreased miR-22 expression. To characterize the upstream promoter region of miR-22, we utilized rapid amplification of cDNA ends and identified the transcription start site and the putative promoter region of miR-22. Mechanistically, we determined that Twist, in combination with HDAC1 and DNMT3B, transcriptionally upregulates miR-22 expression by binding to E-boxes in the proximal miR-22 promoter. We also established that miR-22 causes an increase in growth in 3D but not 2D cultures. Importantly, we observed a direct correlation between increased breast cancer grade and Twist and miR-22 expression. We also identified two potential miR-22 binding sites in the 3'-UTR region of ER and confirmed by promoter assays that miR-22 regulates ER expression by binding to both target sites. These results reveal a novel pathway of ER suppression by Twist through miR-22 activation that could potentially promote the ER negative phenotype in breast cancers.

Indexed as

Breast NeoplasmsEstrogen Receptor alphaFemaleHumansMCF-7 CellsMicroRNAsNeoplasm ProteinsNuclear ProteinsRNA, NeoplasmTwist-Related Protein 1ESR1 protein, humanEstrogen Receptor alphaMicroRNAsMIRN22 microRNA, humanNeoplasm ProteinsNuclear ProteinsRNA, NeoplasmTWIST1 protein, humanTwist-Related Protein 1breast cancerDNMT3BE-boxestrogen receptorHDAC1miR-22promoter UTRtranscriptional regulationTwist

Identifiers

PMID33582945
PMCPMC9128495
OpenAlexW3129669007

What OpenQuestion holds

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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.