shortening of 3′utrs correlates with poor prognosis in breast and lung cancer缩短3u2032utr与不良预后相关的乳腺癌和肺癌.pdfVIP

Shortening of 39UTRs Correlates with Poor Prognosis in Breast and Lung Cancer Antonio Lembo, Ferdinando Di Cunto, Paolo Provero* Department of Genetics, Biology and Biochemistry and Molecular Biotechnology Center, University of Turin, Turin, Italy Abstract A major part of the post-transcriptional regulation of gene expression is affected by trans-acting elements, such as microRNAs, binding the 39 untraslated region (UTR) of their target mRNAs. Proliferating cells partly escape this type of negative regulation by expressing shorter 39 UTRs, depleted of microRNA binding sites, compared to non-proliferating cells. Using large-scale gene expression datasets, we show that a similar phenomenon takes place in breast and lung cancer: tumors expressing shorter 39 UTRs tend to be more aggressive and to result in shorter patient survival. Moreover, we show that a gene expression signature based only on the expression ratio of alternative 3 9 UTRs is a strong predictor of survival in both tumors. Genes undergoing 39UTR shortening in aggressive tumors of the two tissues significantly overlap, and several of them are known to be involved in tumor progression. However the pattern of 39 UTR shortening in aggressive tumors in vivo is clearly distinct from analogous patterns involved in proliferation and transformation. Citation: Lembo A, Di Cunto F, Provero P (2012) Shortening of 39UTRs Correlates with Poor Prognosis in Breast and Lung Cancer. PLoS ONE 7(2): e31129. doi:10.1371/journal.pone.0031129 Editor: Jun Li, Sun Yat-sen University Medical School, China Received August 12, 2011; Accepted January 3, 2012; Published February 8, 2012 Copyright: 2012 Lembo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrest