Inhibition of osteosarcoma by European Mistletoe derived val-miR218.

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Medicinal plants like *Viscum album* L. are explored for novel therapeutic compounds.
• Plant-derived microRNAs (miRNAs) are emerging as bioactive ingredients with potential health benefits.
• Mistletoe contains numerous miRNAs implicated in various human diseases, including cancer.

Purpose of the Study:

• To investigate the anti-cancer activity of mistletoe-derived microRNA val-miR218 against osteosarcoma.
• To elucidate the molecular mechanisms underlying val-miR218's anti-cancer effects.
• To assess the therapeutic potential of val-miR218 in preclinical cancer models.

Main Methods:

• RNA sequencing to identify val-miR218 targets.
• RT-qPCR and western blot to confirm target gene and protein expression.
• Dual-luciferase assay to validate miRNA-target interactions.
• In vivo studies to evaluate anti-tumor efficacy in osteosarcoma models.

Main Results:

• Val-miR218 demonstrated significant anti-cancer effects against osteosarcoma cells.
• Identified 61 direct target genes of val-miR218 involved in cell cycle and DNA replication.
• Val-miR218 inhibited cell growth and induced G0/G1 phase arrest in osteosarcoma cells.
• Mistletoe extracellular vesicles facilitated val-miR218 uptake and enhanced its anti-tumor activity in vivo.

Conclusions:

• Val-miR218 exhibits potent anti-proliferative effects on osteosarcoma cells in vitro and in vivo.
• Plant-derived miRNAs represent a promising therapeutic avenue for cancer treatment, addressing challenges in conventional chemotherapy.
• Mistletoe-derived val-miR218 holds significant therapeutic potential for osteosarcoma and other cancers.