title: Identification of let-7-regulated oncofetal genes.
abstract: MicroRNAs (miRNA) are small RNA molecules of approximately 20 to 22 nucleotides that reduce expression of proteins through mRNA degradation and/or translational silencing. Each known miRNA has a large number of predicted targets. Members of the let-7/miR-98 family of miRNAs are up-regulated at the end of embryonic development. Let-7 is often down-regulated early during cancer development, suggesting that let-7-regulated oncofetal genes (LOG) may become reexpressed in cancer cells. Using comparative bioinformatics, we have identified 12 conserved LOGs that include HMGA2 and IMP-1/CRD-BP. IMP-1 has growth-promoting activities through stabilization of c-myc mRNA. We experimentally confirmed that IMP-1 is a direct let-7 target that promotes cell growth and motility of tumor cells, and we confirmed by proteomics analysis that IMP-1 and HMGA2 are major miRNA targets. Our data suggest that a substantial part of the growth inhibitory activities of let-7 comes from suppressing the expression of IMP-1. LOGs could be novel therapeutic targets and potential biomarkers for cancer treatment.
authors.affiliation: The Ben May Department for Cancer Research, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Boyerinas
authors.forename: Sun-Mi
authors.initials: SM
authors.lastname: Park
authors.forename: Noam
authors.initials: N
authors.lastname: Shomron
authors.forename: Mads M
authors.initials: MM
authors.lastname: Hedegaard
authors.forename: Jeppe
authors.initials: J
authors.lastname: Vinther
authors.forename: Jens S
authors.initials: JS
authors.lastname: Andersen
authors.forename: Christine
authors.initials: C
authors.lastname: Feig
authors.forename: Jinbo
authors.initials: J
authors.lastname: Xu
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Burge
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Peter
mesh_terms: D000230:Adenocarcinoma; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics; D002455:Cell Division; D045744:Cell Line, Tumor; D002465:Cell Movement; D017931:DNA Primers; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D000951:Antigens, Neoplasm; D017931:DNA Primers; D035683:MicroRNAs; D012333:RNA, Messenger; C487931:mirnlet7 microRNA, human; C031192:oncofetal antigens