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 language | English |
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Journal | Cancer Research |
Volume | 68 |
Issue number | 8 |
Pages (from-to) | 2587-2591 |
Number of pages | 4 |
ISSN | 0008-5472 |
DOIs | |
Publication status | Published - 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