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

Mohamad Moustafa Ali, Vijay Suresh Akhade, Subazini Thankaswamy Kosalai, Santhilal Subhash, Luisa Statello, Matthieu Meryet-Figuiere, Jonas Abrahamsson, Tanmoy Mondal and Chandrasekhar Kanduri ()
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Mohamad Moustafa Ali: University of Gothenburg
Vijay Suresh Akhade: University of Gothenburg
Subazini Thankaswamy Kosalai: University of Gothenburg
Santhilal Subhash: University of Gothenburg
Luisa Statello: University of Gothenburg
Matthieu Meryet-Figuiere: University of Gothenburg
Jonas Abrahamsson: University of Gothenburg
Tanmoy Mondal: University of Gothenburg
Chandrasekhar Kanduri: University of Gothenburg

Nature Communications, 2018, vol. 9, issue 1, 1-20

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-03265-1

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