Let-7 Represses Carcinogenesis and a Stem Cell Phenotype in the Intestine via Regulation of Hmga2

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Cancer develops following multiple genetic mutations (i.e. in tumor suppressors and oncogenes), and mutations that cooperate or synergize are often advantageous to cancer cell growth. To study how multiple genes might cooperate, it is usually informative to generate candidate mutations in cells or in mice. Large gene families, such as the Let-7 family, are difficult to silence or mutate because of the large amount of redundancy that exists between similar copies of the same gene; the mutation of one will often be masked or compensated by the continued function of others. In the mouse intestine we have achieved comprehensive depletion of all Let-7 miRNAs in this large multi-genic family through use of an inhibitory protein, called LIN28B, that specifically represses Let-7, and genetic inactivation of another gene cluster called MirLet7c-2/Mirlet7b. Mice with this comprehensive depletion of Let-7 develop intestinal cancers that resemble human colon cancers. Our further analysis identified another gene, HMGA2, downstream of this pathway that is critical to this outcome.

Vyšlo v časopise: Let-7 Represses Carcinogenesis and a Stem Cell Phenotype in the Intestine via Regulation of Hmga2. PLoS Genet 11(8): e32767. doi:10.1371/journal.pgen.1005408
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005408

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