title: Identification of miR-145 targets through an integrated omics analysis.
abstract: MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and protein synthesis. To characterize functions of miRNAs and to assess their potential applications, we carried out an integrated multi-omics analysis to study miR-145, a miRNA that has been shown to suppress tumor growth. We employed gene expression profiling, miRNA profiling and quantitative proteomic analysis of a pancreatic cancer cell line. In our transcriptomic analysis, overexpression of miR-145 was found to suppress the expression of genes that are implicated in development of cancer such as ITGA11 and MAGEA4 in addition to previously described targets such as FSCN1, YES1 and PODXL. Based on miRNA profiling, overexpression of miR-145 also upregulated other miRNAs including miR-124, miR-133b and miR-125a-3p, all of which are implicated in suppression of tumors and are generally co-regulated with miR-145 in other cancers. Using the SILAC system, we identified miR-145-induced downregulation of several oncoproteins/cancer biomarkers including SET, RPA1, MCM2, ABCC1, SPTBN1 and SPTLC1. Luciferase assay validation carried out on a subset of downregulated candidate targets confirmed them to be novel direct targets of miR-145. Overall, this multi-omics approach provided insights into miR-145-mediated tumor suppression and could be used as a general strategy to study the targets of individual miRNAs.
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Tai-Chung
authors.initials: TC
authors.lastname: Huang
authors.forename: Santosh
authors.initials: S
authors.lastname: Renuse
authors.forename: Sneha
authors.initials: S
authors.lastname: Pinto
authors.forename: Praveen
authors.initials: P
authors.lastname: Kumar
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Raghothama
authors.initials: R
authors.lastname: Chaerkady
authors.forename: Brian
authors.initials: B
authors.lastname: Godsey
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Mendell
authors.forename: Marc K
authors.initials: MK
authors.lastname: Halushka
authors.forename: Curt I
authors.initials: CI
authors.lastname: Civin
authors.forename: Luigi
authors.initials: L
authors.lastname: Marchionni
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Pandey
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D019295:Computational Biology / Q000379:methods; D015536:Down-Regulation; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D023281:Genomics / Q000379:methods; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D020543:Proteome; D040901:Proteomics / Q000379:methods; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome
chemical_list: C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D020543:Proteome; D012333:RNA, Messenger