Identification of let-7-regulated oncofetal genes

Benjamin Boyerinas, Sun-Mi Park, Noam Shomron, Mads M Hedegaard, Jeppe Vinther, Jens S Andersen, Christine Feig, Jinbo Xu, Christopher B Burge, Marcus E Peter

Research output: Contribution to journalJournal articleResearchpeer-review

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.
Original languageEnglish
JournalCancer Research
Volume68
Issue number8
Pages (from-to)2587-2591
Number of pages4
ISSN0008-5472
DOIs
Publication statusPublished - 15. Apr 2008

Keywords

  • Adenocarcinoma
  • Animals
  • Antigens, Neoplasm
  • Cell Division
  • Cell Line, Tumor
  • Cell Movement
  • DNA Primers
  • Gene Expression Regulation
  • Gene Silencing
  • Humans
  • Lung Neoplasms
  • Mice
  • MicroRNAs
  • Polymerase Chain Reaction
  • RNA, Messenger
  • Transcription, Genetic

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