title: 3'UTR shortening identifies high-risk cancers with targeted dysregulation of the ceRNA network.
abstract: Competing endogenous RNA (ceRNA) interactions form a multilayered network that regulates gene expression in various biological pathways. Recent studies have demonstrated novel roles of ceRNA interactions in tumorigenesis, but the dynamics of the ceRNA network in cancer remain unexplored. Here, we examine ceRNA network dynamics in prostate cancer from the perspective of alternative cleavage and polyadenylation (APA) and reveal the principles of such changes. Analysis of exon array data revealed that both shortened and lengthened 3'UTRs are abundant. Consensus clustering with APA data stratified cancers into groups with differing risks of biochemical relapse and revealed that a ceRNA subnetwork enriched with cancer genes was specifically dysregulated in high-risk cancers. The novel connection between 3'UTR shortening and ceRNA network dysregulation was supported by the unusually high number of microRNA response elements (MREs) shared by the dysregulated ceRNA interactions and the significantly altered 3'UTRs. The dysregulation followed a fundamental principle in that ceRNA interactions connecting genes that show opposite trends in expression change are preferentially dysregulated. This targeted dysregulation is responsible for the majority of the observed expression changes in genes with significant ceRNA dysregulation and represents a novel mechanism underlying aberrant oncogenic expression.
authors: 1] Key Laboratory of Systems Biology, Shanghai Advanced Research Institute, Chinese Academy of Sciences [2].
authors: Li
authors: L
authors: Li
authors: 1] College of Computer Science and Technology, Jilin University [2].
authors: Duolin
authors: D
authors: Wang
authors: 1] Key Laboratory of Systems Biology, Shanghai Advanced Research Institute, Chinese Academy of Sciences [2].
authors: Mengzhu
authors: M
authors: Xue
authors: Key Laboratory of Systems Biology, Shanghai Advanced Research Institute, Chinese Academy of Sciences.
authors: Xianqiang
authors: X
authors: Mi
authors: College of Computer Science and Technology, Jilin University.
authors: Yanchun
authors: Y
authors: Liang
authors: 1] Key Laboratory of Systems Biology, Shanghai Advanced Research Institute, Chinese Academy of Sciences [2] School of Life Science and Technology, ShanghaiTech University.
authors: Peng
authors: P
authors: Wang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D001483:Base Sequence; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D018390:Gene Targeting / Q000379:methods; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D011471:Prostatic Neoplasms / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics*; D018570:Risk Assessment; D017423:Sequence Analysis, RNA / Q000379:methods*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D005819:Genetic Markers; D035683:MicroRNAs; D012334:RNA, Neoplasm