title: MicroRNA target prediction by expression analysis of host genes.
abstract: MicroRNAs (miRNAs) are small noncoding RNAs that control gene expression by inducing RNA cleavage or translational inhibition. Most human miRNAs are intragenic and are transcribed as part of their hosting transcription units. We hypothesized that the expression profiles of miRNA host genes and of their targets are inversely correlated and devised a novel procedure, HOCTAR (host gene oppositely correlated targets), which ranks predicted miRNA target genes based on their anti-correlated expression behavior relative to their respective miRNA host genes. HOCTAR is the first tool for systematic miRNA target prediction that utilizes the same set of microarray experiments to monitor the expression of both miRNAs (through their host genes) and candidate targets. We applied the procedure to 178 human intragenic miRNAs and found that it performs better than currently available prediction softwares in pinpointing previously validated miRNA targets. The high-scoring HOCTAR predicted targets were enriched in Gene Ontology categories, which were consistent with previously published data, as in the case of miR-106b and miR-93. By means of overexpression and loss-of-function assays, we also demonstrated that HOCTAR is efficient in predicting novel miRNA targets and we identified, by microarray and qRT-PCR procedures, 34 and 28 novel targets for miR-26b and miR-98, respectively. Overall, we believe that the use of HOCTAR significantly reduces the number of candidate miRNA targets to be tested compared to the procedures based solely on target sequence recognition. Finally, our data further confirm that miRNAs have a significant impact on the mRNA levels of most of their targets.
authors.affiliation: Telethon Institute of Genetics and Medicine (TIGEM), 80131 Naples, Italy.
authors.forename: Vincenzo Alessandro
authors.initials: VA
authors.lastname: Gennarino
authors.forename: Marco
authors.initials: M
authors.lastname: Sardiello
authors.forename: Raffaella
authors.initials: R
authors.lastname: Avellino
authors.forename: Nicola
authors.initials: N
authors.lastname: Meola
authors.forename: Vincenza
authors.initials: V
authors.lastname: Maselli
authors.forename: Santosh
authors.initials: S
authors.lastname: Anand
authors.forename: Luisa
authors.initials: L
authors.lastname: Cutillo
authors.forename: Andrea
authors.initials: A
authors.lastname: Ballabio
authors.forename: Sandro
authors.initials: S
authors.lastname: Banfi
mesh_terms: D000465:Algorithms; D005544:Forecasting / Q000379:methods; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology*; D005796:Genes; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D017423:Sequence Analysis, RNA / Q000379:methods
chemical_list: D035683:MicroRNAs