Cascade DNA Logic Strategy for Profiling the MiRNA-210-Targeted Signaling Pathway in the Warburg Effect of Triple-Negative Breast Cancer

The Warburg effect, a hallmark of cancer, entails a metabolic shift from oxidative phosphorylation to aerobic glycolysis and is tightly regulated by complex signaling pathways. Decoding the dynamic signaling pathways underlying oncogenic metabolic reprogramming remains a major analytical challenge. Here, we report a cascaded DNA logic gate strategy capable of profiling the miR-210/CYGB/p53 axis that regulates the Warburg effect in triple-negative breast cancer (TNBC) cells. By logically integrating an H2O2-responsive DNAzyme (Dz) module with an entropy-driven reaction (EDR), the INHIBIT-AND logic device simultaneously interrogates upstream (miR-210) and downstream (CYGB mRNA, H2O2) effectors, producing dual amplified fluorescent outputs in response to specific pathway states. This programmable system enables live-cell, logic-based decoding of the Warburg effect, distinguishing TNBC from other breast cancer subtypes and dynamically reflecting pathway modulation. Our approach establishes a generalizable framework for using molecular computation to analyze complex biological circuits, providing a powerful tool for precision pathway profiling and therapeutic strategy development.