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

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 of CHEK1 with prolonged relapse-free survival (RFS) of luminal BC patients treated with adjuvant chemotherapy. In patients with luminal A subtype treated with neoadjuvant therapy, the opposite role for RFS was seen 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 ER+ MCF-7 cell line. In summary, we have identified the association of a 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE267543 | GEO | 2025/05/15

REPOSITORIES: GEO

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