Activation of an endogenous retrovirus-associated long non-coding RNA in XXXX @entity420 .

@entity1 @entity5 @entity71290 @entity14 @entity420
BACKGROUND: Long non-coding RNAs (lncRNAs) are emerging as molecules that significantly impact many cellular processes and have been associated with almost every @entity1 @entity5 . Compared to protein-coding genes, lncRNA genes are often associated with transposable elements, particularly with endogenous retroviral elements (ERVs). ERVs can have potentially deleterious effects on genome structure and function, so these elements are typically silenced in normal somatic tissues, albeit with varying efficiency. The aberrant regulation of ERVs associated with lncRNAs (ERV-lncRNAs), coupled with the diverse range of lncRNA functions, creates significant potential for ERV-lncRNAs to impact @entity5 biology. METHODS: We used RNA-seq analysis to identify and profile the expression of a novel lncRNA in six large cohorts, including over 7,500 samples from The @entity5 (TCGA). RESULTS: We identified the @entity5 -specific expression of a novel lncRNA that we have named Endogenous retroViral-associated @entity420 RNA or ' @entity71290 ', by analyzing RNA-seq data derived from @entity14 and matched normal control tissues. Subsequent analysis of TCGA RNA-seq data revealed the striking association of @entity71290 with @entity420 , which are @entity5 of glandular origin. Moderate to high levels of @entity71290 were detected in 25 to 53% of colon, rectal, lung, pancreas and @entity420 (mean   =   30 to 144 FPKM), and @entity71290 expression correlated with decreased @entity1 survival (Cox regression; hazard ratio   =   1.47, 95% confidence interval   =   1.06 to 2.04, P   =   0.02). In @entity5 sites of non-glandular origin, @entity71290 expression was detectable at only very low levels and in less than 10% of @entity1 . For @entity71290 , a MER48 ERV element provides an active promoter to drive its transcription. Genome-wide, MER48 insertions are associated with nine lncRNAs, but none of the MER48-associated lncRNAs other than @entity71290 were consistently expressed in @entity420 , demonstrating the specific activation of @entity71290 . The sequence and structure of the @entity71290 locus is highly conserved among Old World monkeys and apes but not New World monkeys or prosimians, where the MER48 insertion is absent. Conservation of the @entity71290 locus suggests a functional role for this novel lncRNA in @entity1 and our closest primate relatives. CONCLUSIONS: Our results describe the specific activation of a highly conserved ERV-lncRNA in numerous @entity5 of glandular origin, a finding with diagnostic, prognostic and therapeutic implications.
