A Novel Cross-Kingdom Regulatory Mode of Thermostable miR166 from Taraxacum mongolicum Inhibits HepG2 Cell Proliferation in Association with Downregulation of the Candidate Target STAP2

Taraxacum mongolicum contains various bioactive components. This study investigated the potential of thermostable microRNAs (miRNAs) derived from this plant as cross-kingdom regulators and evaluated their anti-proliferative effects on HepG2 cells. High-throughput sequencing was used to screen thermostable miRNAs and predict their target genes. Enrichment and target gene expression in gavaged mice were analyzed to assess cross-kingdom regulatory potential. Cellular assays evaluated anti-proliferative activity. miR166 was identified as a thermostable miRNA in T. mongolicum, and bioinformatics indicated its possible involvement in cancer-associated mucin-type O-glycan biosynthesis. RT-qPCR revealed that miR166 was negatively correlated with signal transducing adaptor family member 2 (STAP2) mRNA expression. In mice, administration of total RNA extracted from fresh T. mongolicum or its water decoction led to significant changes in miR166 levels in stomach, blood, liver, spleen, and intestine, accompanied by reduced STAP2 mRNA, suggesting cross-kingdom regulation. Overexpression of miR166 induced a delay in G1/S transition in HepG2 cells in a concentration-dependent manner, accompanied by reduced STAP2 expression and decreased cell viability. These findings provide preliminary experimental evidence that thermostable miR166 from T. mongolicum is associated with inhibition of HepG2 proliferation. They also suggest STAP2 as a candidate regulatory target, offer a potential new molecule for further investigation in liver cancer intervention, and provide a preliminary molecular basis for the medicinal and edible value of T. mongolicum.