Integrative miRNOMe profiling reveals the miR-195-5p-CHEK1 axis and its impact on luminal breast cancer outcomes
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F75010330%3A_____%2F25%3A00015037" target="_blank" >RIV/75010330:_____/25:00015037 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11120/25:43928597 RIV/00216208:11130/25:10497379 RIV/00216208:11140/25:10497379 RIV/70883521:28150/25:63594818 RIV/00064203:_____/25:10497379
Result on the web
<a href="https://febs.onlinelibrary.wiley.com/doi/10.1002/1878-0261.70077" target="_blank" >https://febs.onlinelibrary.wiley.com/doi/10.1002/1878-0261.70077</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/1878-0261.70077" target="_blank" >10.1002/1878-0261.70077</a>
Alternative languages
Result language
angličtina
Original language name
Integrative miRNOMe profiling reveals the miR-195-5p-CHEK1 axis and its impact on luminal breast cancer outcomes
Original language description
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 similar to 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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30204 - Oncology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Molecular Oncology
ISSN
1574-7891
e-ISSN
1878-0261
Volume of the periodical
19
Issue of the periodical within the volume
11
Country of publishing house
US - UNITED STATES
Number of pages
18
Pages from-to
3409-3426
UT code for WoS article
001513100900001
EID of the result in the Scopus database
2-s2.0-105008753747