Splicing towards noncoding isoforms in colorectal carcinoma is associated with tumor hypoxia and the DNA damage response

Tumor hypoxia is associated with poor patient outcome and resistance to therapy. It is associated with a rapid decline in protein production mediated through mTOR signalling. Here we show that it also leads to widespread changes in splicing and a global shift towards the expression of noncoding isoforms, thus providing a novel and orthogonal mechanism by which cells can modulate protein expression. Overall design: Examination of mRNA levels in HCT116 cells after 0 hr, 1 hr, 2 hr and 24 hr in hypoxia. Three biological replicates each.

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Memon D, Dawson K, Smowton CS, Xing W, Dive C, Miller CJ