Evidence map›Paper›PMID 40548926›Full record

ArticleMolecular oncology2025

Integrative miRNOMe profiling reveals the miR-195-5p-CHEK1 axis and its impact on luminal breast cancer outcomes.

Veronika Boušková, Marie Ehrlichová, Alžběta Spálenková, Ivona Krus, Simona Šůsová, Viktor Hlaváč, Vlasta Němcová, Renata Koževnikovová, Markéta Trnková, David Vrána and 5 more

Abstract read
In one paragraph

Article in Molecular oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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

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4 · The record

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5 · Who and what money

Authors and funding

15 authors.

Veronika BouškováToxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic.ORCID 0000-0002-0758-4657
Marie EhrlichováToxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic.
Alžběta SpálenkováToxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic.
Ivona KrusToxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic.
Simona ŠůsováToxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic.
Viktor HlaváčToxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic.
Vlasta NěmcováDepartment of Biochemistry, Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
Renata KoževnikovováMEDICON a.s., Prague, Czech Republic.
Markéta TrnkováUnilabs Pathology k.s., Prague, Czech Republic.
David VránaComprehensive Cancer Center of Hospital AGEL Novy Jicin, Czech Republic.
Jiří GatěkEUC Hospital Zlin and Tomas Bata University in Zlin, Czech Republic.
Kateřina KopečkováDepartment of Oncology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
Marcela MrhalováDepartment of Pathology and Molecular Medicine, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
Soňa MěšťákováDepartment of Surgery, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
Pavel SoučekToxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic.ORCID 0000-0002-4294-6799

Funding

Czech health research council NU22-08-00281European Union - Next Generation EU LX22NPO5102Grant Agency of Charles University in Prague 207043
6 · The paper itself

Abstract

The luminal subtype (estrogen receptor-positive, ER+) is the most common and the most heterogeneous type of breast carcinoma (BC) in women. During our study, we determined expression levels of all microRNAs (miRNome) in 101 ER+ BC samples and identified 25 miRNAs being associated with proliferative markers. Using comprehensive in silico analyses we prioritized CHEK1, CDC25A, and CCNE1 as candidate genes affecting the proliferation of ER+ BC, with two microRNAs from the miR-497∼195 cluster identified as their potential regulators. In a cohort of 217 patients, we found a significant association between high expression of CHEK1 and shorter relapse-free survival (RFS) in luminal BC patients treated with adjuvant chemotherapy, especially in patients with luminal A subtype. In patients treated with neoadjuvant therapy, the opposite role for RFS was observed for hsa-miR-195-5p. Subsequently, we confirmed the potency of hsa-miR-195-5p to inhibit the expression of CHEK1 in vitro. Moreover, the specific Chk1 inhibitor rabusertib (LY2603618) significantly enhanced the efficacy of doxorubicin in both ER+ and ER- cell lines. In summary, we have identified the association of a specific miRNA profile with highly proliferative luminal BCs and demonstrated the ability of hsa-miR-195-5p to inhibit CHEK1 expression in BC in vitro, underlining the importance of CHEK1 expression and its inhibition for prognosis and treatment of patients with luminal BCs.

Indexed as

Breast NeoplasmsCheckpoint Kinase 1Gene Expression ProfilingMicroRNAsCell Line, TumorCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansMiddle AgedTreatment OutcomeCheckpoint Kinase 1CHEK1 protein, humanMicroRNAsMIRN195 microRNA, humanbreast carcinomachemotherapyDNA damage responseluminal subtypemicroRNAprognosis

Identifiers

PMID40548926
PMCPMC12591302

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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.