Prognostic value of ZEB1 and its association with miR-7641 in triple-negative breast cancer: a correlative and in vitro study.

چکیده اصلی

BACKGROUND: Triple-negative breast cancer (TNBC) is characterised by the absence of specific therapeutic targets and a high tendency for metastasis. This research explored the clinical relevance and functional interaction between the EMT regulator ZEB1 and the oncomir miR-7641 in the progression of TNBC. METHODS: We analysed ZEB1 expression in the triple-negative breast cancer (TNBC) subset of the TCGA-BRCA cohort. A cohort of 60 TNBC patients was used to validate ZEB1 and miR-7641 expression via qRT-PCR and IHC. Associations with clinicopathological parameters were assessed. In vitro, loss-of-function and rescue experiments were conducted in TNBC cell lines to evaluate the functional relationship between miR-7641 and ZEB1. RESULTS: ZEB1 and miR-7641 were co-overexpressed in TNBC tissues and metastatic subgroups. Elevated expression of both molecules is associated with advanced TNM stage, lymphovascular invasion, lymph node metastasis, and reduced survival. Functionally, ZEB1 knockdown inhibited malignant behaviours, but this inhibition was rescued by miR-7641 overexpression, indicating a functional interdependence between the two molecules rather than a simple unidirectional regulatory relationship. CONCLUSIONS: The co-overexpression of ZEB1 and miR-7641 characterises an aggressive TNBC subtype with poor prognosis. Our findings reveals a significant positive expression correlation and functional interdependence between miR-7641 and ZEB1 in metastatic TNBC, this molecule pair represents a promising candidate prognostic biomarker panel, while the underlying molecular regulatory mechanism requires further rigorous validation.

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