Targeting KRAS Regulation with PolyPurine Reverse Hoogsteen Oligonucleotides

Categories: Notícies

The KRAS gene is GC-rich, containing regions with known and putative G-quadruplex (G4) forming regions. The Cancer therapy group in collaboration with researchers from Binghamton University, tested different designs of KRAS Polypurine Reverse Hoogsteen hairpins (PPRHs) targeting the KRAS complementary sequences of putative G4 regions within the promoter, intron 1 and exon 5 regions to downregulate KRAS transcription and mediating an anti-proliferative effect. G4 formations were tested by circular dichroism and confirmed by gel electrophoresis using Thioflavin T. The effect on KRAS transcription was examined by luciferase, FRET Melt2, qRT-PCR. Cytotoxicity was evaluated in pancreatic and ovarian cancer cells. PPRHs bound selectively to their target regions and stabilize G4 formation within KRAS and represent an innovative approach to both G4-stabilization and to KRAS modulation with potential for novel therapeutics.

Targeting KRAS Regulation with PolyPurine Reverse Hoogsteen OligonucleotidesPsaras, A.M., Valiuska, S., Noé, V., Ciudad, C.J., Brooks, T.A. International Journal of Molecular Sciences. 2022, 23(4), 2097