PAN-cancer analysis of S-phase enriched IncRNAs identifies oncogenic drivers and biomarkers

Despite improvement in our understanding of long noncoding RNAs (IncRNAs) role in cancer, efforts to find clinically relevant cancer-associated IncRNAs are still lacking. Here, using nascent RNA capture sequencing, we identify 1145 temporally expressed S-phase-enriched IncRNAs. Among these, 570 IncRNAs show significant differential expression in at least one tumor type across TCGA data sets. Systematic clinical investigation of 14 Pan-Cancer data sets identified 633 independent prognostic markers. Silencing of the top differentially expressed and clinically relevant S-phase-enriched IncRNAs in several cancer models affects crucial cancer cell hallmarks. Mechanistic investigations on SCAT7 in multiple cancer types reveal that it interacts with hnRNPK/YBX1 complex and affects cancer cell hallmarks through the regulation of FGF/FGFR and its downstream PI3K/AKT and MAPK pathways. We also implement a LNA-antisense oligo-based strategy to treat cancer cell line and patient-derived tumor (PDX) xenografts. Thus, this study provides a comprehensive list of IncRNA-based oncogenic drivers with potential prognostic value.