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

Author

Listed:
  • 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)

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.

Suggested Citation

  • Mohamad Moustafa Ali & Vijay Suresh Akhade & Subazini Thankaswamy Kosalai & Santhilal Subhash & Luisa Statello & Matthieu Meryet-Figuiere & Jonas Abrahamsson & Tanmoy Mondal & Chandrasekhar Kanduri, 2018. "PAN-cancer analysis of S-phase enriched lncRNAs identifies oncogenic drivers and biomarkers," Nature Communications, Nature, vol. 9(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03265-1
    DOI: 10.1038/s41467-018-03265-1
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