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Gene expression

FLI1 circRNA FECR1 drives metastasis

Chen N, Zhao G, Yan X, et al. · Genome biology · 2018

Open access · cc by · source: Europe PMC

Exonic circular RNA FECR1 binds the FLI1 promoter and epigenetically activates FLI1 in breast cancer.

Study at a glance

Design
Animal / in-vitro — dCas9 CasIP and functional assays of FECR1 circRNA in MDA-MB231 cells
N
Cell-line mechanistic study; no single primary analytic N in stored text
Population
MDA-MB231 breast cancer cells (with tumor vs adjacent FLI1 context)
Outcome
FECR1 activation of FLI1 and invasive phenotypes

Structured fields used in claim comparison tables when every cited study has a complete layer.

Key findings

FECR1 is a FLI1 exonic circRNA that activates FLI1 epigenetically and promotes invasive phenotypes; FLI1 is elevated in tumor vs adjacent tissue.

Methodology

Used dCas9 chromatin immunoprecipitation (CasIP) in MDA-MB231 cells to pull RNAs at the FLI1 promoter, then tested FECR1 function and TET1/DNMT1 regulation.

Limitations

Not a clinical trial of circRNA therapy; human data are observational staining/expression.

How this study connects

Role on claims

Each row is a claim on a concept or method page where this paper supports, challenges, or qualifies the statement. Roles are hand-checked — not a model guess.

  • SupportsGene expressionconcept

    FECR1 is a FLI1 exonic circRNA that activates FLI1 epigenetically and promotes invasive phenotypes; FLI1 is elevated in tumor vs adjacent tissue.

    Evidence for the claim as stated.

  • Several papers tagged for this method barely use qPCR as the headline assay. Cryptosporidium oocyst work is a transcriptome of environmental persistence; FECR1 function was tested with dCas9 chromatin immunoprecipitation and TET1/DNMT1 regulation in MDA-MB231 cells; rice histone Kbu/Kcr maps came from mass spectrometry and ChIP-seq. Any qPCR in those studies is at most a supporting check.

    Evidence for the claim as stated.

  • Lexicon tagging also pulls in studies whose core methods are RNA-seq, CasIP or ChIP-seq/MS. Cryptosporidium metabolic inferences, FECR1 promoter RNA pull-downs, and rice histone acylations should not be read as qPCR papers that measured the same class of target.

    Evidence for the claim as stated.

  • Catalytically dead Cas9 can be used as a locus-specific hook. dCas9 chromatin immunoprecipitation (CasIP) in MDA-MB231 cells pulled RNAs at the FLI1 promoter and helped identify FECR1, a FLI1 exonic circRNA that activates FLI1 and promotes invasion — a dCas9 affinity experiment, not a knockout screen.

    Evidence for the claim as stated.

  • The strongest tension is naming. The 2007 array paper and the Listeria pan-genome treat CRISPR as a genomic feature of bacteria; the Cas13a and dCas9 papers treat CRISPR–Cas as a laboratory tool. Both usages are historically connected, but a finding about repeat RNA folding does not license a claim about editing a human promoter, and a CasIP result does not catalogue environmental CRISPR diversity.

    Evidence for the claim as stated.

  • Even among tool papers, the enzyme is not always Cas9 cutting DNA. Cas13a targets RNA viruses; dCas9 in CasIP binds without requiring a cut. Calling every experiment a 'CRISPR knockout' is false for this set.

    Evidence for the claim as stated.

  • SupportsBisulfite Sequencingmethod

    FECR1, a FLI1 exonic circular RNA, was recovered by dCas9 chromatin immunoprecipitation at the FLI1 promoter in MDA-MB231 cells, activates FLI1 via TET1/DNMT1 regulation, and promotes invasive phenotypes, with FLI1 elevated in tumour versus adjacent tissue. That is CasIP and chromatin-modifier genetics, not a bisulfite methylome; human data are observational staining/expression, not a circRNA therapy trial.

    Evidence for the claim as stated.

  • SupportsBisulfite Sequencingmethod

    FECR1 is a false-positive or peripheral hit for bisulfite sequencing: promoter RNA pull-down and TET1/DNMT1 regulation of FLI1, not a converted-cytosine map. Citing it as a methylome paper confuses chromatin RNA occupancy with CpG calls.

    Evidence for the claim as stated.

  • SupportsChIP-seqmethod

    FECR1 was identified by dCas9 chromatin immunoprecipitation (CasIP) of RNAs at the FLI1 promoter in MDA-MB231 cells, then shown to activate FLI1 epigenetically via TET1/DNMT1 and to promote invasion, with FLI1 higher in tumour than adjacent tissue. CasIP is occupancy of RNA at a locus, not a histone-mark ChIP-seq atlas, and human data are observational.

    Evidence for the claim as stated.

  • SupportsChIP-seqmethod

    Only the rice histone-acylation paper is clearly genome-wide ChIP-seq of chromatin marks (Kbu/Kcr versus H3K9ac under stress). Foxp3 work is candidate-locus ChIP; FECR1 is CasIP of promoter RNAs; Yoruba data are 27K methylation arrays. Treating them as one ChIP-seq method overstates shared technology.

    Evidence for the claim as stated.

  • SupportsChIP-seqmethod

    What 'epigenetic activation' means also disagrees. Rice Kcr occupancy resembles acetylation and moves with metabolic stress but is not proven necessary at each site. FECR1 recruits TET1/DNMT1 logic at FLI1. Foxp3 stability tracks TSDR demethylation rather than a mapped histone peak. Those are different causal sketches.

    Evidence for the claim as stated.

Open questions

Tensions this paper is part of

From concept pages' “where studies disagree.” Disagreement means the same question; scope means different assays, populations, or outcomes.

  • Scope difference — different assays, populations, or outcomes

    Lexicon tagging also pulls in studies whose core methods are RNA-seq, CasIP or ChIP-seq/MS. Cryptosporidium metabolic inferences, FECR1 promoter RNA pull-downs, and rice histone acylations should not be read as qPCR papers that measured the same class of target.

  • Scope difference — different assays, populations, or outcomes

    The strongest tension is naming. The 2007 array paper and the Listeria pan-genome treat CRISPR as a genomic feature of bacteria; the Cas13a and dCas9 papers treat CRISPR–Cas as a laboratory tool. Both usages are historically connected, but a finding about repeat RNA folding does not license a claim about editing a human promoter, and a CasIP result does not catalogue environmental CRISPR diversity.

  • Scope difference — different assays, populations, or outcomes

    Even among tool papers, the enzyme is not always Cas9 cutting DNA. Cas13a targets RNA viruses; dCas9 in CasIP binds without requiring a cut. Calling every experiment a 'CRISPR knockout' is false for this set.

    Also on this tension

  • Scope difference — different assays, populations, or outcomes

    FECR1 is a false-positive or peripheral hit for bisulfite sequencing: promoter RNA pull-down and TET1/DNMT1 regulation of FLI1, not a converted-cytosine map. Citing it as a methylome paper confuses chromatin RNA occupancy with CpG calls.

  • Scope difference — different assays, populations, or outcomes

    SupportsChIP-seq

    Only the rice histone-acylation paper is clearly genome-wide ChIP-seq of chromatin marks (Kbu/Kcr versus H3K9ac under stress). Foxp3 work is candidate-locus ChIP; FECR1 is CasIP of promoter RNAs; Yoruba data are 27K methylation arrays. Treating them as one ChIP-seq method overstates shared technology.

  • Scope difference — different assays, populations, or outcomes

    SupportsChIP-seq

    What 'epigenetic activation' means also disagrees. Rice Kcr occupancy resembles acetylation and moves with metabolic stress but is not proven necessary at each site. FECR1 recruits TET1/DNMT1 logic at FLI1. Foxp3 stability tracks TSDR demethylation rather than a mapped histone peak. Those are different causal sketches.

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Same topic cluster — not a recommendation engine.