Association of lncRNA AGAP11 with prognosis and malignant progression in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is aggressive with poor prognosis and limited reliable prognostic markers.

Objectives

This study investigated the association between long non-coding RNA (lncRNA) ArfGAP With GTPase Domain, Ankyrin Repeat and PH Domain 11 (AGAP11) expression and clinicopathological characteristics and prognosis of early-stage TNBC patients, along with experimental validation of the regulatory effect of AGAP11 on TNBC cell malignancy and the tumor microenvironment through targeting miR-1269a.

Methods

This retrospective study examined 126 early-stage TNBC patients. AGAP11 and miR-1269a expression levels were detected using quantitative polymerase chain reaction (qPCR). The clinical significance of AGAP11 was analyzed. The impact of AGAP11 overexpression alone and in conjunction with miR-1269a overexpression, on the behavior of TNBC cells and the tumor microenvironment was examined.

Results

AGAP11 was down-regulated in TNBC tissues and cells (P < 0.001). Low AGAP11 expression was significantly associated with adverse clinicopathological characteristics (P < 0.05). Low AGAP11 was an independent risk factor for poor prognosis (HR = 0.254, P = 0.006) and predicted worse 5-year survival (P = 0.003). AGAP11 overexpression inhibited TNBC cell malignant activity (P < 0.05), and disrupted the homeostasis of the tumor microenvironment (P < 0.05). MiR-1269a was up-regulated in TNBC (P < 0.001). AGAP11 directly binds miR-1269a, and miR-1269a co-overexpression reversed inhibitory effects by AGAP11 (P < 0.05). Conclusion AGAP11 is a potential prognostic biomarker for TNBC and an important parameter for clinical stratification. Through the AGAP11/miR-1269a axis, it regulates TNBC cell behavior and the tumor microenvironment, which offers new insights for precision diagnosis and treatment.