Evidence map›Paper›PMID 39725737›Full record

ArticleCellular and molecular life sciences : CMLS2024

The splicing machinery is dysregulated and represents a therapeutic vulnerability in breast cancer.

Natalia Hermán-Sánchez, Miguel E G-García, Juan M Jiménez-Vacas, Elena M Yubero-Serrano, Laura M López-Sánchez, Sara Romero-Martín, Jose L Raya-Povedano, Marina Álvarez-Benito, Justo P Castaño, Raúl M Luque and 1 more

Abstract read
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

11 authors.

Natalia Hermán-Sánchez *Maimónides Institute of Biomedical Research of Córdoba (IMIBIC), IMIBIC building. Av. Menéndez Pidal s/n, Córdoba, 14004, Spain.
Miguel E G-García *Maimónides Institute of Biomedical Research of Córdoba (IMIBIC), IMIBIC building. Av. Menéndez Pidal s/n, Córdoba, 14004, Spain.
Juan M Jiménez-VacasMaimónides Institute of Biomedical Research of Córdoba (IMIBIC), IMIBIC building. Av. Menéndez Pidal s/n, Córdoba, 14004, Spain.
Elena M Yubero-SerranoMaimónides Institute of Biomedical Research of Córdoba (IMIBIC), IMIBIC building. Av. Menéndez Pidal s/n, Córdoba, 14004, Spain.
Laura M López-SánchezMaimónides Institute of Biomedical Research of Córdoba (IMIBIC), IMIBIC building. Av. Menéndez Pidal s/n, Córdoba, 14004, Spain.
Sara Romero-MartínMaimónides Institute of Biomedical Research of Córdoba (IMIBIC), IMIBIC building. Av. Menéndez Pidal s/n, Córdoba, 14004, Spain.
Jose L Raya-PovedanoMaimónides Institute of Biomedical Research of Córdoba (IMIBIC), IMIBIC building. Av. Menéndez Pidal s/n, Córdoba, 14004, Spain.
Marina Álvarez-BenitoMaimónides Institute of Biomedical Research of Córdoba (IMIBIC), IMIBIC building. Av. Menéndez Pidal s/n, Córdoba, 14004, Spain.
Justo P CastañoMaimónides Institute of Biomedical Research of Córdoba (IMIBIC), IMIBIC building. Av. Menéndez Pidal s/n, Córdoba, 14004, Spain. justo@uco.es.
Raúl M LuqueMaimónides Institute of Biomedical Research of Córdoba (IMIBIC), IMIBIC building. Av. Menéndez Pidal s/n, Córdoba, 14004, Spain. bc2luhur@uco.es.
Manuel D GaheteMaimónides Institute of Biomedical Research of Córdoba (IMIBIC), IMIBIC building. Av. Menéndez Pidal s/n, Córdoba, 14004, Spain. bc2gaorm@uco.es.ORCID http://orcid.org/0000-0002-4578-2179

Funding

Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y NutriciónConsejería de Salud y Familias, Junta de Andalucía BIO-0139Consejería de Salud y Familias, Junta de Andalucía PEMP-0036-2020Fundación Científica Asociación Española Contra el Cáncer INVES18Instituto de Salud Carlos III PI20/01301Instituto de Salud Carlos III PI23/00652Ministerio de Ciencia, Innovación y Universidades BFU2010-19300Ministerio de Ciencia, Innovación y Universidades FPU20/03954Ministerio de Ciencia, Innovación y Universidades FPU20/03957Ministerio de Ciencia, Innovación y Universidades PID2022-1381850B-I00
6 · The paper itself

Abstract

Breast cancer (BCa) is a highly prevalent pathological condition (̴30% in women) with limited and subtype-dependent prognosis and therapeutic options. Therefore, BCa management might benefit from the identification of novel molecular elements with clinical potential. Since splicing process is gaining a great relevance in cancer, this work analysed the expression of multiple Spliceosome Components (SCs = 17) and Splicing Factors (SFs = 26) and found a drastic dysregulation in BCa (n = 69) vs. control (negative biopsies; n = 50) samples. Among all the components analysed, we highlight the upregulation of ESRP1 and down-regulation of PRPF8 and NOVA1 in BCa vs. control samples. Indeed, ESRP1 was specially overexpressed in triple-negative BCa (TNBCa) and associated with worse prognosis (i.e., higher BCa grade and lower overall survival), suggesting an association of ESRP1 with BCa aggressiveness. On the other hand, PRPF8 expression was generally downregulated in BCa with no associations to clinical characteristics, while NOVA1 expression was lower in TNBCa patients and highly aggressive tumours. Consistently, NOVA1 overexpression in vitro reduced functional parameters of aggressiveness in ER-/PR- cell lines (MDA-MB-231 and BT-549) but not in ER+/PR+ cells (MCF7), suggesting a critical role of NOVA1 in subtype-specific BCa. Finally, the in vitro pharmacological inhibition of splicing machinery using pladienolide B decreased aggressiveness features in all the BCa cell lines, showing a subtype-independent inhibitory potential, but being relatively innocuous in normal-like breast cells. These results demonstrate the profound dysregulation of the splicing machinery in BCa and their potential as source of promising diagnosis/prognosis markers, as well as valuable therapeutic targets for BCa.

Indexed as

Breast NeoplasmsNeuro-Oncological Ventral AntigenRNA-Binding ProteinsRNA SplicingAgedCell Line, TumorEpoxy CompoundsFemaleGene Expression Regulation, NeoplasticHumansMacrolidesMiddle AgedPrognosisPyransRNA Splicing FactorsSpliceosomesEpoxy CompoundsESRP1 protein, humanMacrolidesNeuro-Oncological Ventral AntigenNOVA1 protein, humanpladienolide BPyransRNA-Binding ProteinsRNA Splicing FactorsBreast cancerHormone receptorNOVA1Pharmacological inhibitionPladienolide BSplicing

Identifiers

PMID39725737
PMCPMC11671448

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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.