Laminar double hydroxide-loaded miR-654-3p targets POU2F1-mediated metabolic reprogramming against colorectal cancer.

Colorectal cancer (CRC), a major malignancy of the digestive system, poses a serious threat to human health. Metabolic reprogramming is a hallmark of cancer, promoting tumor growth and metastasis by altering the energy metabolism of tumor cells and reshaping the tumor microenvironment (TME). MicroRNAs with high expression levels play critical roles in the TME. In this study, miRNA-seq detected low expression of miR-654-3p in plasma exosomes from CRC patient samples. The molecular mechanism of miR-654-3p in CRC was analyzed and verified through in vivo and in vitro experiments. The results showed that miR-654-3p targeted POU2F1-mediated metabolic reprogramming to inhibit autophagy and epithelial-mesenchymal transition (EMT) in CRC. Furthermore, layered double hydroxide (LDH) nanoparticles were synthesized to construct LDH@miR-654-3p nanocomposites. This system was used to further elucidate the molecular mechanism of miR-654-3p in CRC, demonstrating the antitumor efficacy of LDH-loaded miR-654-3p and clarifying its underlying mechanisms. These findings provide a theoretical basis for the clinical translation of this nanotherapeutic strategy in CRC treatment.