Plant-derived miRNAs: Cross-kingdom anti-tumor agents and next generation of oral biopharmaceuticals.

In recent years, plant-derived microRNAs (miRNAs), as a new type of cross-kingdom regulatory molecules, have shown great potential in anti-tumor therapy. These non-coding RNAs, about 20-24 nucleotides (nt) long, can stably exist in the human body through dietary intake and resist nuclease degradation through unique protective mechanisms, thereby achieving cross-kingdom gene regulation. Studies show that they can directly target tumor-related signaling pathways to inhibit cancer cell proliferation and induce apoptosis and indirectly exert anti-tumor effects by regulating long non-coding RNAs and immune cell functions in the tumor microenvironment. However, oral delivery faces multiple biological barriers. Researchers have developed innovative delivery strategies to improve miRNA stability, targeting, and bioavailability. Despite its promising application, clinical translation is limited. Future efforts should combine multi-omics technologies, optimize delivery systems, and adopt synergistic therapy to promote it as an oral anti-tumor biologic.