Identification of let-7-regulated oncofetal genes.
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.
Boyerinas
Benjamin
B
The Ben May Department for Cancer Research, University of Chicago, Chicago, Illinois 60637, USA.
Park
Sun-Mi
SM
Shomron
Noam
N
Hedegaard
Mads M
MM
Vinther
Jeppe
J
Andersen
Jens S
JS
Feig
Christine
C
Xu
Jinbo
J
Burge
Christopher B
CB
Peter
Marcus E
ME
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
D000951:Antigens, Neoplasm; D017931:DNA Primers; D035683:MicroRNAs; D012333:RNA, Messenger; C487931:mirnlet7 microRNA, human; C031192:oncofetal antigens