Putative G‑Quadruplex Structures in Dysregulated Long Non-coding RNA of Ovarian Cancer and Their Binding Interactions...

Long noncoding RNAs (lncRNAs) influence the progression, metastasis, and drug resistance of various cancers including ovarian cancer (OC). Putative G-quadruplex (G4)-forming sequences that are abundant in cancer-dysregulated lncRNAs have not been systematically pursued from a structure-function correlation perspective. In this work, we have used a combination of informatics, computational tools, spectroscopy, and molecular biology experiments to identify G4 formation by the OC-dysregulated lncRNAs ERLNC1, DLX6-AS1, LINC01127, FMNL1-DT, and LINP1. The in vitro ability of the lncRNAs to fold into G4 structures was accompanied by interesting profiles of individual G-tract contributions and response to monovalent cations, ligand TMPyP4, and G4-targeting antibody. Human serum albumin (HSA) was found to interact with these G4-forming lncRNAs, albeit with different affinities and structural implications for the G4 motifs. The G4-motif likely plays a crucial role in the binding interactions of select lncRNAs with HSA. This study provides the first systematic study of putative G4-forming sequences in OC-dysregulated lncRNAs and elucidates their interactions with HSA. The interaction of lncRNAs with HSA, possibly facilitated by G4 motifs, can be valuable for OC diagnosis and therapeutics.