Evidence map›Paper›PMID 41150697›Full record

ArticlePLoS biology2025

PRMT5 regulates alternative splicing of TCF3 under hypoxia to promote EMT and invasion in breast cancer.

Srinivas Abhishek Mutnuru, Pooja Yadav, Parik Kakani, Shruti Ganesh Dhamdhere, Poorva Kumari, Shruti Agrawal, Atul Samaiya, Sanjeev Shukla

Abstract read
In one paragraph

Article in PLoS biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Srinivas Abhishek MutnuruDepartment of Biological Sciences, Indian Institute of Science Education and Research Bhopal, Bhopal, Madhya Pradesh, India.
Pooja YadavDepartment of Biological Sciences, Indian Institute of Science Education and Research Bhopal, Bhopal, Madhya Pradesh, India.
Parik KakaniDepartment of Biological Sciences, Indian Institute of Science Education and Research Bhopal, Bhopal, Madhya Pradesh, India.
Shruti Ganesh DhamdhereDepartment of Biological Sciences, Indian Institute of Science Education and Research Bhopal, Bhopal, Madhya Pradesh, India.
Poorva KumariDepartment of Biological Sciences, Indian Institute of Science Education and Research Bhopal, Bhopal, Madhya Pradesh, India.
Shruti AgrawalDepartment of Pathology, Bansal Hospital, Bhopal, Madhya Pradesh, India.
Atul SamaiyaDepartment of Surgical Oncology, Bansal Hospital, Bhopal, Madhya Pradesh, India.
Sanjeev ShuklaDepartment of Biological Sciences, Indian Institute of Science Education and Research Bhopal, Bhopal, Madhya Pradesh, India.ORCID 0000-0003-3361-0588

Funding

Council of Scientific and Industrial Research fellowship, IndiaDepartment of Biotechnology (DBT, India)Indian Institute of Science Education and Research-Bhopal, India
6 · The paper itself

Abstract

Tumor hypoxia induced alterations in the epigenetic landscape and alternative splicing influence cellular adaptations. PRMT5 is a type II protein arginine methyltransferase that regulates several tumorigenic events in many cancer types. However, the regulation of PRMT5 and its direct implication on aberrant alternative splicing under hypoxia remains unexplored. In this study, we observed hypoxia-induced upregulation of PRMT5 via the CTCF in human breast cancer cells. Further, PRMT5-mediated symmetric arginine dimethylation H4R3me2s and H3R8me2s directly regulated the alternative splicing of TCF3. Under hypoxia, PRMT5-mediated histone dimethylation at the intronic conserved region (ICR) present between TCF3 exon 18a and exon 18b recruits DNMT3A, resulting in DNA methylation. DNA methylation at the TCF3-ICR is recognized and bound by MeCP2 resulting in RNA-Pol II pausing, promoting the recruitment of the negative splicing factor PTBP1 to the splicing locus of TCF3 pre-mRNA. PTBP1 promotes the exclusion of exon 18a which results in the production of the pro-invasive TCF3-18B (E47) isoform which promotes EMT and invasion of breast cancer cells under hypoxia. Collectively, our results indicate PRMT5-mediated symmetric arginine dimethylation of histones regulates alternative splicing of TCF3 gene thereby enhancing EMT and invasion in breast cancer hypoxia.

Indexed as

Alternative SplicingBasic Helix-Loop-Helix ProteinsBreast NeoplasmsEpithelial-Mesenchymal TransitionProtein-Arginine N-MethyltransferasesCCCTC-Binding FactorCell HypoxiaCell Line, TumorDNA MethylationDNA Methyltransferase 3AExonsFemaleGene Expression Regulation, NeoplasticHistonesHumansMCF-7 CellsBasic Helix-Loop-Helix ProteinsCCCTC-Binding FactorCTCF protein, humanDNA Methyltransferase 3ADNMT3A protein, humanHistonesPRMT5 protein, humanProtein-Arginine N-MethyltransferasesRepressor ProteinsTCF3 protein, human

Identifiers

PMID41150697
PMCPMC12585103

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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.