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

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00216208:11120/25:43928597 RIV/00216208:11130/25:10497379 RIV/00216208:11140/25:10497379 RIV/70883521:28150/25:63594818 RIV/00064203:_____/25:10497379

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Molecular Oncology

ISSN

1574-7891

e-ISSN

1878-0261

Svazek periodika

19

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

18

Strana od-do

3409-3426

Kód UT WoS článku

001513100900001

EID výsledku v databázi Scopus

2-s2.0-105008753747