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

Nature Communications
Mohamad Moustafa AliChandrasekhar Kanduri

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.

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Datasets Mentioned

BETA
GSE92250

Methods Mentioned

BETA
RNA-seq
antisense oligonucleotides
flow cytometry
PCR
transfection
pull-down
immunoprecipitation
ChIP
RIP
pull-downs

Software Mentioned

LifeScope
HISAT
Survival package
BedTools
GENCODE
Trimmomatic
HISAT aligner
Short Time - series Expression Miner ( STEM )
COSMIC
count

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