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

Journal article
Authors Moustafa Ali Mohamad
Vijay Suresh Akhade
Subazini Thankaswamy Kosalai
Santhilal Subhash
Luisa Statello
Meryet-Figuiere Matthieu
Jonas Abrahamsson
Tanmoy Mondal
Chandrasekhar Kanduri
Published in Nature Communications
Volume 9
Issue 1
ISSN 2041-1723
Publication year 2018
Published at Institute of Clinical Sciences, Department of Pediatrics
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Language en
Keywords Cancer, lncRNAs, Cell cycle, TCGA
Subject categories Cell and Molecular Biology


Despite improvement in our understanding of long noncoding RNAs (lncRNAs) role in cancer, efforts to find clinically relevant cancer-associated lncRNAs are still lacking. Here, using nascent RNA capture sequencing, we identify 1145 temporally expressed S-phase-enriched lncRNAs. Among these, 570 lncRNAs 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 lncRNAs 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 lncRNA-based oncogenic drivers with potential prognostic value.

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