RESUMEN
Triple-negative breast cancer (TNBC) has high malignancy and limited treatment, so novel molecular therapeutic targets are urgently needed. Cyclin E1 (CCNE1) promotes progression in breast cancer, but its role and inherent mechanisms in TNBC are yet to be elucidated. Competing endogenous RNA (ceRNA) may be a potential mechanism. CCNE1 was selected though bioinformatics and clinical samples, and cell lines were utilized to verify CCNE1 expression by qRT-PCR and western blot. Predicting tools provided potential miR-195-5p and SENP3-EIF4A1 and tested from multilevel. Functional experiments were conducted in vitro and in vivo. Luciferase reporter assay and RNA immunoprecipitation experiments were implemented to ensure the interaction between miR-195-5p and SENP3-EIF4A1/CCNE1 in TNBC. Bioinformatics found DNA hypermethylation of miR-195-5p and preliminarily verified. Mechanistically, SENP3-EIF4A1-miR-195-5p-associated ceRNA could drive TNBC progress though regulating CCNE1. DNA hypermethylation of miR-195-5p might be another reason. In summary, SENP3-EIF4A1-miR-195-5p-CCNE1 axis promotes TNBC progress and may contribute to the novel diagnosis and treatment of TNBC.
RESUMEN
The tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation proteins (14-3-3) participate in the tumorigenesis and progression of numerous malignances, but their precise prognostic values in breast cancer (BrCa) remain unknown. Here, we investigated the expression profiles and prognostic roles of 14-3-3 isoforms by employing multiple online databases. The transcriptional levels of most 14-3-3 isoforms in BrCa tissues were significantly higher than those in normal tissues. High mRNA expression of 14-3-3 beta/sigma/theta/zeta was significantly associated with poor overall survival (OS) in BrCa patients, while high mRNA expression of 14-3-3 epsilon was notably related to favorable OS. High mRNA expression of 14-3-3 beta/gamma/sigma/theta/zeta was significantly associated with poor relapse-free survival (RFS) in BrCa patients. A high mutation rate of 14-3-3 was determined to be associated with poor clinical outcomes. In addition, 14-3-3 expression was correlated with the infiltration of specific immune cells types. Analysis of the breast-specific protein-protein interaction (PPI) network suggested that 14-3-3 proteins were involved in several potential oncogenic mechanisms in BrCa. Finally, we performed experimentally validated their oncogenic roles in BrCa. Overall, our findings systematically elucidate the expression and distinct prognostic value of 14-3-3 isoforms in BrCa, which may provide potential therapeutic targets and prognostic biomarkers for BrCa.