Putative G-Quadruplex Structures in Dysregulated Long Non-coding RNA of Ovarian Cancer and Their Binding Interactions with Human Serum Albumin

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.