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

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. 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. 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. 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.