期刊
NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-03265-1
关键词
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资金
- Knut and Alice Wallenberg Foundation (KAW) [Dnr KAW 2014.0057]
- Swedish Foundation for Strategic Research [RB13-0204]
- Swedish Cancer Research foundation (Cancerfonden: Kontrakt) [150796]
- Swedish Research Council [2017-02834]
- Barncancerfonden [PR2016-0057]
- Ingabritt Och Arne Lundbergs forskningsstiftelse
- RNATRAIN-Marie-Curie ITN (EU FP7)
- LUA/ALF
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.
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