Isoimperatorin suppresses triple-negative breast cancer by modulating miR-874-3p/POU2F1 axis: a new avenue for metabolic and redox intervention.

Abstract

BACKGROUND: Metabolic alterations are key factors driving the development of breast cancer. Among them, metabolic reprogramming is an important biological hallmark of breast cancer. It is crucial to gain in-depth understanding of the relevant mechanisms and find effective treatment strategies. Isoimperatorin (ISO), a natural furanocoumarin, exhibits various pharmacological effects such as anti-inflammatory and antiviral activities. However, the impact of ISO on the growth of breast cancer cells and its underlying mechanisms remain unclear. METHODS: Cell culture, transfection, and animal experiments were employed. CCK -8, colony formation, and flow cytometry were used to detect cell proliferation, apoptosis, and ROS levels. miRNA-Seq, qRT-PCR, and Western Blotting were applied to analyze gene and protein expression. RESULTS: ISO inhibited breast cancer cell proliferation, induced apoptosis and ROS accumulation, and suppressed the Warburg effect. ISO upregulated miR- 874-3p, which directly targeted the 3′-UTR of POU2F1, inhibiting the transcriptional activation of key glycolytic genes. Blocking this axis reversed ISO’s tumor-suppressive effects in vitro and in vivo. CONCLUSION: This study first reveals a novel mechanism by which ISO regulates breast cancer metabolism and apoptosis via the miR-874-3p/POU2F1 axis, highlighting ISO’s potential as a dual metabolic-redox intervention agent and providing a new combined therapeutic target for breast cancer.