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Colorectal cancer (CRC) remains a major contributor to cancer-related mortality. LIN28A and LIN28B are highly related RNA-binding protein paralogs that regulate biogenesis of let-7 microRNAs and influence development, metabolism, tissue regeneration, and oncogenesis. Here we demonstrate that overexpression of either LIN28 paralog cooperates with the Wnt pathway to promote invasive intestinal adenocarcinoma in murine models. When LIN28 alone is induced genetically, half of the resulting tumors harbor Ctnnb1 (β-catenin) mutation. When overexpressed in Apc(Min/+) mice, LIN28 accelerates tumor formation and enhances proliferation and invasiveness. In conditional genetic models, enforced expression of a LIN28-resistant form of the let-7 microRNA reduces LIN28-induced tumor burden, while silencing of LIN28 expression reduces tumor volume and increases tumor differentiation, indicating that LIN28 contributes to tumor maintenance. We detected aberrant expression of LIN28A and/or LIN28B in 38% of a large series of human CRC samples (n = 595), where LIN28 expression levels were associated with invasive tumor growth. Our late-stage CRC murine models and analysis of primary human tumors demonstrate prominent roles for both LIN28 paralogs in promoting CRC growth and progression and implicate the LIN28/let-7 pathway as a therapeutic target.
Pubmed ID: 25956904 RIS Download
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The aim of the project is to provide contemporary estimates of the incidence of, mortality and prevalence from major types of cancer, at national level, for 184 countries of the world. The GLOBOCAN estimates are presented for 2012, separately for each sex. 1-, 3- and 5-year prevalence data are available for the adult population only (ages 15 and over). Please note that: These estimates are based on the most recent data available at IARC and on information publically available on the Internet, but more recent figures may be available directly from local sources. Because the sources of data are continuously improving in quality and extent, estimates may not be truly comparable overtime and care should be taken when comparing these estimates with those published earlier. The observed differences may be the result of a change in the methodology and should not be interpreted as a time trend effect.
View all literature mentionsAn efficient software tool to utilize update-to-date information to functionally annotate genetic variants detected from diverse genomes (including human genome hg18, hg19, as well as mouse, worm, fly, yeast and many others). Given a list of variants with chromosome, start position, end position, reference nucleotide and observed nucleotides, ANNOVAR can perform: 1. gene-based annotation. 2. region-based annotation. 3. filter-based annotation. 4. other functionalities. (entry from Genetic Analysis Software)
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Tg(Vil1-cre)997Gum/J from IMSR.
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