Abstract
The microRNA let-7 regulates late embryonic development by suppressing expression of a number of genes such as c-myc and RAS as well as the embryonic gene high mobility group, A2 (HMGA2). We now demonstrate that HMGA2 is more efficiently targeted by let-7 than RAS. Its expression inversely correlates with the expression of let-7 in the NCI60 cells lines, and the expression of RAS does not change when amounts of let-7 that efficiently silence expression of HMGA2 are introduced into tumor cells. We did not find a difference in the expression of HMGA2 between primary ovarian cancer samples and matching metastases, suggesting that the expression of HMGA2 represents an early event during cancer progression. The late repression of HMGA2 by let-7 during embryonic development, and the early reexpression of HMGA2 during cancer development, is in line with the hypothesis that cancer development represents a case of reverse embryogenesis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2585-2590 |
| Number of pages | 6 |
| Journal | Cell Cycle |
| Volume | 6 |
| Issue number | 21 |
| DOIs | |
| State | Published - Nov 1 2007 |
Funding
supported by the Ovarian Cancer Research Members of the let-7/miR-98 family10-15 are induced late in mammalian embryonic Fund (Liz Tilberis Scholars Program) and development suppressing expression of embryonic genes that are not expressed in the NIH grants R01 CA111882 (to E.L.) and adult organism. Reported let-7 targets include RAS, c-myc and HMGA2.15-20Let-7 is R01 GM61712 ©2007 LANDES BIOSCIENCE(to M.E.P). 12-15,17 frequently downregulated in human neoplasms, suggesting that embryonic target genes of let-7 may be upregulated in cancer. We have recently provided the first direct link in a human cancer between downregulation of let-7 and upregulation of HMGA2.17
Keywords
- Metastasis
- Ovarian cancer
- Reverse embryogenesis
- Supercluster
- microRNA
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
- Developmental Biology
