Cellular modulation of a G-quadruplex structure found in the lung cancer-related microRNA-3196.

Fiche publication

Date publication

juin 2025

Journal

International journal of biological macromolecules

Auteurs

Membres identifiés du Cancéropôle Est :
Dr MONCHAUD David

Tous les auteurs :
Alexandre D, Polido J, Miranda A, Hudson RHE, Monchaud D, Baptista PV, Cruz C

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/40527376

Résumé

RNA G-quadruplexes (G4s) are promising drug targets due to their high cellular abundance. G-rich RNA regions inherently form G4 structures, while GC-rich sequences adopt stem-loop conformations, and their dynamic equilibrium critically influences RNA function. MicroRNAs (miRs), key regulators of protein expression, undergo processing by Dicer, which specifically recognizes stem-loop structures in precursor miRs (pre-miRs). Notably, some pre-miRs containing G4-forming sequences influence Dicer cleavage, suggesting that G4s can directly regulate miR production. Moreover, pre-miRs with G4 structures present promising targets for small molecules. This research focuses on identifying and modulating G4 structure in pre-miR-3196 to restore normal lung cancer (LC) levels, offering a potential therapeutic strategy. Firstly, bioinformatic analysis confirmed the presence of G4 motifs in pre-miR-3196, and confocal imaging validated G4 formation in cells. Subsequently, further confirmation came from a combination of biophysical and biochemical assays. Additionally, cellular studies with and without the RNA G4 destabilizer PhpC, revealed that miR-3196 biogenesis is modulated by the G4-stem-loop equilibrium in specific pre-miRs. These findings highlighted the possibility of using G4 to control the expression of mature miR-3196 and revealed the potential of employing the destabilizer PhpC to adjust its G4 structure.