Targeted inhibition of oncogenic microRNAs provides a promising anti-cancer approach. Here, we report a bifunctional chimera for ligand-directed regulation of target oncogenic precursor microRNA through photo-degradation. Chimeric TGP-210-Ppa with photosensitizer pyropheophorbide a (Ppa) linked with the ligand of the oncogenic precursor miR-210 was able to bind specifically to oncogenIc pre-miRNA and produce 1 O 2 under red light irradiation to degrade the target pre-miRNA. This bifunctional chimera-based modification of precursor microRNA serves as a unique method for target gene regulation since photo-irradiation was able to provide temporal-spatial resolution. We demonstrated that TGP-210-Ppa prevented the generation of functional miR-210 in breast cancer cells in a photocontrollable manner. This also successfully reversed the downstream oncogenic signaling pathway mediated by miR-210 to promote cancer cell death.
Keyphrases
- transcription factor
- cell proliferation
- long non coding rna
- cell death
- signaling pathway
- long noncoding rna
- photodynamic therapy
- highly efficient
- oxidative stress
- cell therapy
- pi k akt
- radiation induced
- stem cells
- papillary thyroid
- induced apoptosis
- bone marrow
- cell cycle arrest
- endoplasmic reticulum stress
- mesenchymal stem cells
- childhood cancer