Evidence map›Paper›PMID 41455985›Full record

ArticleCell communication and signaling : CCS2025

Strongly regulated transcription factors exert an outsized influence in microRNA-regulated networks.

Laura Sourdin, Julie M Bracken, Philip A Gregory, Nora Feldker, Thomas Brabletz, Simone Brabletz, Yeesim Khew-Goodall, Gregory J Goodall, Katherine A Pillman, Cameron P Bracken

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell communication and signaling : CCS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
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.

Laura Sourdin *Centre for Cancer Biology, An Alliance of SA Pathology and University of South Australia, Bradley Building, North Terrace, Adelaide, SA, 5000, Australia.
Julie M BrackenCentre for Cancer Biology, An Alliance of SA Pathology and University of South Australia, Bradley Building, North Terrace, Adelaide, SA, 5000, Australia.
Philip A GregoryCentre for Cancer Biology, An Alliance of SA Pathology and University of South Australia, Bradley Building, North Terrace, Adelaide, SA, 5000, Australia.
Nora FeldkerDepartment of Experimental Medicine 1, Nikolaus-Fiebiger-Center for Molecular Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
Thomas BrabletzDepartment of Experimental Medicine 1, Nikolaus-Fiebiger-Center for Molecular Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
Simone BrabletzDepartment of Experimental Medicine 1, Nikolaus-Fiebiger-Center for Molecular Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
Yeesim Khew-GoodallCentre for Cancer Biology, An Alliance of SA Pathology and University of South Australia, Bradley Building, North Terrace, Adelaide, SA, 5000, Australia.
Gregory J GoodallCentre for Cancer Biology, An Alliance of SA Pathology and University of South Australia, Bradley Building, North Terrace, Adelaide, SA, 5000, Australia.
Katherine A Pillman *Centre for Cancer Biology, An Alliance of SA Pathology and University of South Australia, Bradley Building, North Terrace, Adelaide, SA, 5000, Australia. katherine.pillman@unisa.edu.au.
Cameron P Bracken *Centre for Cancer Biology, An Alliance of SA Pathology and University of South Australia, Bradley Building, North Terrace, Adelaide, SA, 5000, Australia. cameron.bracken@unisa.edu.au.

Funding

Australian Research Council FT190100544Cancer Council Australia PRF2518Hospital Research Foundation 2023-S-DTFA-001-83100Kids' Cancer Project Col Reynolds FellowshipNational Breast Cancer Foundation IIRS18147National Health and Medical Research Council 1128479Worldwide Cancer Research WCR-19-0300
6 · The paper itself

Abstract

Identifying the most biologically meaningful microRNA (miRNA) targets remains challenging, as predictive and biochemical methods yield many weak or non-productive interactions. Transcription factors (TFs) are enriched among miRNA targets and amplify miRNA effects through their broad regulatory influence. Frequently, these same TFs also regulate the miRNA, forming double negative feedback loops that enforce bistable gene expression and cell-fate decisions. We investigated this regulatory motif by focusing on reciprocal repression between the miR-200 family and ZEB1/2, which governs epithelial-mesenchymal plasticity. Employing a system isolating ZEB-dependent effects of miR-200c and combining Weighted Gene Co-expression Network Analysis (WGCNA) with Exon-Intron Split Analysis (EISA), as well as functional cell biology assays, we show this circuit reinforces mutually exclusive epithelial and mesenchymal states through complex networks of intertwined direct and indirect, transcriptional and post-transcriptional, ZEB-dependent and independent mechanisms. Our findings highlight how miRNA-TF feedback loops can act as bistable switches to lock cell identity and emphasize the pivotal role of strongly regulated TFs within miRNA target networks.

Indexed as

Gene Regulatory NetworksMicroRNAsTranscription FactorsEpithelial-Mesenchymal TransitionHomeodomain ProteinsHumansZinc Finger E-box-Binding Homeobox 1Zinc Finger E-box Binding Homeobox 2Homeodomain ProteinsMicroRNAsMIRN200 microRNA, humanTranscription FactorsZEB1 protein, humanZEB2 protein, humanZinc Finger E-box-Binding Homeobox 1Zinc Finger E-box Binding Homeobox 2Bi-stable switchGene regulationMicroRNAMiR-200Transcription factor

Identifiers

PMID41455985
PMCPMC12853912

What Socratic 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 Socratic graph.