| publication name | Nucleic Acid Targeted Therapy: G4 Oligonucleotides Downregulate HRAS in Bladder Cancer Cells through a Decoy Mechanism. ACS Med. Chem. Lett., (2015), 6 (12), 1179-1183 |
|---|---|
| Authors | Giulia Miglietta; Alaa S. Gouda; Susanna Cogoi; Erik B. Pedersen; Luigi E. Xodo. |
| year | 2015 |
| keywords | HRAS, G4-oligonucleotides, anthraquinone insertions, T24 bladder cancer cells, decoy mechanism |
| journal | ACS Med. Chem. Lett. |
| volume | 6 |
| issue | 12 |
| pages | 1179-1183 |
| publisher | American Chemical Society |
| Local/International | International |
| Paper Link | http://pubs.acs.org/doi/abs/10.1021/acsmedchemlett.5b00315 |
| Full paper | download |
| Supplementary materials | Not Available |
Abstract
In a previous study we have demonstrated that two neighboring G-quadruplexes, hras-1 and hras-2, located immediately 16 upstream of the major transcription start site of HRAS, bind MAZ, a nuclear factor that activates transcription (doi: 17 10.1093/nar/gku574). For the present study we have designed G4 oligonucleotides with anthraquinone insertions and locked nucleic 18 acids (LNA) modifications mimicking quadruplex hras-1. Luciferase, qRT-PCR and Western blot data demonstrate that these con19 structs efficiently down regulate HRAS in cancer cells. The inhibitory efficiency of the G4 oligonucleotides correlates with their 20 nuclease resistance in the cell environment. By chromatin immunoprecipitation we show that the association of MAZ to the HRAS 21 promoter is strongly attenuated by the designed G4 oligonucleotides, thus suggesting that these constructs behave with a decoy mechanism