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

Autor:	Ali MM; Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden., Akhade VS; Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden., Kosalai ST; Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden., Subhash S; Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden., Statello L; Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden., Meryet-Figuiere M; Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden., Abrahamsson J; Department of Pediatrics, Institution for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden., Mondal T; Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden., Kanduri C; Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden. kanduri.chandrasekhar@gu.se.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2018 Feb 28; Vol. 9 (1), pp. 883. Date of Electronic Publication: 2018 Feb 28.
DOI:	10.1038/s41467-018-03265-1
Abstrakt:	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.
Databáze:	MEDLINE
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