| Literature DB >> 29785014 |
Hyun Jung Park1,2,3, Ping Ji4, Soyeon Kim5, Zheng Xia1,2, Benjamin Rodriguez1,2, Lei Li1,2, Jianzhong Su1,2, Kaifu Chen1,2, Chioniso P Masamha6, David Baillat4, Camila R Fontes-Garfias4, Ann-Bin Shyu7, Joel R Neilson8, Eric J Wagner9, Wei Li10,11.
Abstract
Widespread mRNA 3' UTR shortening through alternative polyadenylation 1 promotes tumor growth in vivo 2 . A prevailing hypothesis is that it induces proto-oncogene expression in cis through escaping microRNA-mediated repression. Here we report a surprising enrichment of 3'UTR shortening among transcripts that are predicted to act as competing-endogenous RNAs (ceRNAs) for tumor-suppressor genes. Our model-based analysis of the trans effect of 3' UTR shortening (MAT3UTR) reveals a significant role in altering ceRNA expression. MAT3UTR predicts many trans-targets of 3' UTR shortening, including PTEN, a crucial tumor-suppressor gene 3 involved in ceRNA crosstalk 4 with nine 3'UTR-shortening genes, including EPS15 and NFIA. Knockdown of NUDT21, a master 3' UTR-shortening regulator 2 , represses tumor-suppressor genes such as PHF6 and LARP1 in trans in a miRNA-dependent manner. Together, the results of our analysis suggest a major role of 3' UTR shortening in repressing tumor-suppressor genes in trans by disrupting ceRNA crosstalk, rather than inducing proto-oncogenes in cis.Entities:
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Year: 2018 PMID： 29785014 PMCID： PMC6689271 DOI： 10.1038/s41588-018-0118-8
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330