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 journalArticlepeer-review

167 Scopus citations

Abstract

MicroRNAs (miRNA) are small RNA molecules of ∼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 (US)
Pages (from-to)2587-2591
Number of pages5
JournalCancer Research
Volume68
Issue number8
DOIs
StatePublished - Apr 15 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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