LncRNA EILA promotes CDK4/6 inhibitor resistance in breast cancer by stabilizing cyclin E1 protein.

ABSTRACT: CDK4/6 inhibitors (CDK4/6i) plus endocrine therapy are now standard first-line therapy for advanced HR⁺/HER2^- breast cancer, but developing resistance is just a matter of time in these patients. Here, we report that a cyclin E1-interacting lncRNA (EILA) is up-regulated in CDK4/6i-resistant breast cancer cells and contributes to CDK4/6i resistance by stabilizing cyclin E1 protein. EILA overexpression correlates with accelerated cell cycle progression and poor prognosis in breast cancer. Silencing EILA reduces cyclin E1 protein and restores CDK4/6i sensitivity both in vitro and in vivo. Mechanistically, hairpin A of EILA binds to the carboxyl terminus of cyclin E1 protein and hinders its binding to FBXW7, thereby blocking its ubiquitination and degradation. EILA is tran

SUBMITTER: Cai Z 

PROVIDER: S-EPMC10558131 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature