title: Global gene expression analysis reveals reduced abundance of putative microRNA targets in human prostate tumours.
abstract: BACKGROUND
  Recently, microRNAs (miRNAs) have taken centre stage in the field of human molecular oncology. Several studies have shown that miRNA profiling analyses offer new possibilities in cancer classification, diagnosis and prognosis. However, the function of miRNAs that are dysregulated in tumours remains largely a mystery. Global analysis of miRNA-target gene expression has helped illuminate the role of miRNAs in developmental gene expression programs, but such an approach has not been reported in cancer transcriptomics.
  
  
  RESULTS
  In this study, we globally analysed the expression patterns of miRNA target genes in prostate cancer by using several public microarray datasets. Intriguingly, we found that, in contrast to global mRNA transcript levels, putative miRNA targets showed a reduced abundance in prostate tumours relative to benign prostate tissue. Additionally, the down-regulation of these miRNA targets positively correlated with the number of types of miRNA target-sites in the 3' untranslated regions of these targets. Further investigation revealed that the globally low expression was mainly driven by the targets of 36 specific miRNAs that were reported to be up-regulated in prostate cancer by a miRNA expression profiling study. We also found that the transcript levels of miRNA targets were lower in androgen-independent prostate cancer than in androgen-dependent prostate cancer. Moreover, when the global analysis was extended to four other cancers, significant differences in transcript levels between miRNA targets and total mRNA backgrounds were found.
  
  
  CONCLUSIONS
  Global gene expression analysis, along with further investigation, suggests that miRNA targets have a significantly reduced transcript abundance in prostate cancer, when compared with the combined pool of all mRNAs. The abnormal expression pattern of miRNA targets in human cancer could be a common feature of the human cancer transcriptome. Our study may help to shed new light on the functional roles of miRNAs in cancer transcriptomics.
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, PR China. regularhand@gmail.com
authors.forename: Ruping
authors.initials: R
authors.lastname: Sun
authors.forename: Xuping
authors.initials: X
authors.lastname: Fu
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Xie
authors.forename: Yumin
authors.initials: Y
authors.lastname: Mao
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000728:Androgens / Q000378:metabolism; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D000728:Androgens; D035683:MicroRNAs; D012333:RNA, Messenger