Evidence map›Paper›PMID 35130925›Full record

ArticleMolecular cancer2022

Dual CRISPR interference and activation for targeted reactivation of X-linked endogenous FOXP3 in human breast cancer cells.

Xuelian Cui, Chao Zhang, Zhifang Xu, Shuaibin Wang, Xin Li, Erica Stringer-Reasor, Sejong Bae, Leiping Zeng, Dehua Zhao, Runhua Liu and 2 more

Open access · goldAbstract readLetter
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.7field-weighted citation impact, top 5% 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

25 citing papers in PubMed, 44 citations in OpenAlex.

  1. Article
  2. Review
  3. CRISPR Interference to Inhibit Oncogenes for Cancer Therapy.International journal of molecular sciences · 2026
    Review
  4. Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026
    Review
  5. Review
  6. Review
  7. Reversing transgene silencing via targeted chromatin editing.bioRxiv : the preprint server for biology · 2025
    Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Review
  19. CRISPR applications in cancer diagnosis and treatment.Cellular & molecular biology letters · 2023
    Review
  20. Progress and Perspective of CRISPR-Cas9 Technology in Translational Medicine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    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

12 authors at 2 institutions in 1 country.

Xuelian CuiDepartment of Genetics, University of Alabama at Birmingham, 720 20th Street South, Birmingham, AL, 35294, USA.
Chao ZhangDepartment of Genetics, University of Alabama at Birmingham, 720 20th Street South, Birmingham, AL, 35294, USA.
Zhifang XuDepartment of Genetics, University of Alabama at Birmingham, 720 20th Street South, Birmingham, AL, 35294, USA.
Shuaibin WangDepartment of Genetics, University of Alabama at Birmingham, 720 20th Street South, Birmingham, AL, 35294, USA.
Xin LiDepartment of Genetics, University of Alabama at Birmingham, 720 20th Street South, Birmingham, AL, 35294, USA.
Erica Stringer-ReasorDepartment of O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, 720 20th Street South, Birmingham, AL, 35294, USA.
Sejong BaeDepartment of O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, 720 20th Street South, Birmingham, AL, 35294, USA.
Leiping ZengDepartment of Bioengineering, Stanford University, 443 Via Ortega, Stanford, CA, 94305, USA.
Dehua ZhaoDepartment of Bioengineering, Stanford University, 443 Via Ortega, Stanford, CA, 94305, USA.
Runhua LiuDepartment of Genetics, University of Alabama at Birmingham, 720 20th Street South, Birmingham, AL, 35294, USA. runhua@uab.edu.
Lei S QiDepartment of Bioengineering, Stanford University, 443 Via Ortega, Stanford, CA, 94305, USA. stanley.qi@stanford.edu.
Lizhong WangDepartment of Genetics, University of Alabama at Birmingham, 720 20th Street South, Birmingham, AL, 35294, USA. lwang12@uab.edu.ORCID 0000-0003-1980-4730
University of Alabama at Birmingham · USStanford University · US

Funding

XRAY CRYSTALLOGRAPHYP30CA013148 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Robert S Welner · 1985 to 2026
$165.9M
NCI NIH HHS P30 CA013148
6 · The paper itself

Abstract

backgroundUnlike autosomal tumor suppressors, X-linked tumor suppressors can be inactivated by a single hit due to X-chromosome inactivation (XCI). Here, we argue that targeted reactivation of the non-mutated allele from XCI offers a potential therapy for female breast cancers.

methodsTowards this goal, we developed a dual CRISPR interference and activation (CRISPRi/a) approach for simultaneously silencing and reactivating multiple X-linked genes using two orthogonal, nuclease-deficient CRISPR/Cas9 (dCas9) proteins.

resultsUsing Streptococcus pyogenes dCas9-KRAB for silencing XIST and Staphylococcus aureus dCas9-VPR for activating FOXP3, we achieved CRISPR activation of FOXP3 in various cell lines of human female breast cancers. In human breast cancer HCC202 cells, which express a synonymous heterozygous mutation in the coding region of FOXP3, simultaneous silencing of XIST from XCI led to enhanced and prolonged FOXP3 activation. Also, reactivation of endogenous FOXP3 in breast cancer cells by CRISPRi/a inhibited tumor growth in vitro and in vivo. We further optimized CRISPRa by fusing dCas9 to the demethylase TET1 and observed enhanced FOXP3 activation. Analysis of the conserved CpG-rich region of FOXP3 intron 1 confirmed that CRISPRi/a-mediated simultaneous FOXP3 activation and XIST silencing were accompanied by elevated H4 acetylation, including H4K5ac, H4K8ac, and H4K16ac, and H3K4me3 and lower DNA methylation. This indicates that CRISPRi/a targeting to XIST and FOXP3 loci alters their transcription and their nearby epigenetic modifications.

conclusionsThe simultaneous activation and repression of the X-linked, endogenous FOXP3 and XIST from XCI offers a useful research tool and a potential therapeutic for female breast cancers.

Indexed as

Breast NeoplasmsGenes, X-LinkedCell LineDNA MethylationFemaleForkhead Transcription FactorsHumansMixed Function OxygenasesProto-Oncogene ProteinsForkhead Transcription FactorsFOXP3 protein, humanMixed Function OxygenasesProto-Oncogene ProteinsTET1 protein, humanBreast cancerCRISPRFOXP3TranscriptX-linked gene

Identifiers

PMID35130925
PMCPMC8819949
OpenAlexW4210668238

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LicenceCC BY
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Registered trials

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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.