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SUMMARY:Comprehensive transcriptome and epigenome sequencing of hypoxic br
 east cancer reveals non-coding RNAs associated with clinicopathological fe
 atures - Ioannis (Jiannis) Ragoussis\, McGill University\, Canada and Geno
 me Quebec Innovation Centre
DTSTART:20131209T130000Z
DTEND:20131209T140000Z
UID:TALK49089@talks.cam.ac.uk
CONTACT:Laura Blackburn
DESCRIPTION:Hypoxia is an important physiological stress with a central ro
 le in many responses including adaptation to altitude\, growth and develop
 ment\, as well as major pathophysiological processes such as ischaemia and
  cancer. Pan-genomic analyses of these responses have focused on protein-c
 oding genes. However\, it is now recognised that many transcripts have fun
 ctions that do not include coding for proteins (noncoding\nRNA). Here\, we
  comprehensively profile this non-coding transcriptional output in hypoxia
 . We undertook an integrated pan-genomic analysis of normoxic and hypoxic 
 MCF7 breast cancer cells\, employing RNA-seq together with ChIP-seq for th
 e major hypoxia-inducible transcription factor HIF and for chromosomal mar
 kers of active transcription (RNApol2 and histone H3K4 methylation). We fu
 rther assessed these responses following knockdown of HIF transcription fa
 ctors using RNAi. We establish a computational pipeline of strand specific
  ribodepleted RNA-seq data to detect regulated non-coding transcripts incl
 uding piwiRNA\, miRNA\, tRNA\, sn/snoRNA\, and lncRNA. We describe 105 pre
 viously annotated transcripts bearing chromosomal marks of bona-fide genes
 . Four hypoxically induced lncRNAs were then analysed in 148 breast tumour
 s and associated with clinicopathological features. Our findings extend kn
 owledge of the hypoxic transcriptional response into the spectrum of nonco
 ding transcripts. We demonstrate that HIF can transcriptionally activate l
 ncRNAs in addition to coding transcripts and link these to clinicopatholog
 ical features. These HIF-regulated non-coding transcripts have the potenti
 al to act as new biomarkers for breast cancer as well as potentially novel
  therapeutic targets.
LOCATION:Cancer Research UK Cambridge Institute\, Lecture Theatre
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