Let-7 prevents early cancer progression by suppressing expression of the embryonic gene HMGA2
Let-7 prevents early cancer progression by suppressing expression of the embryonic gene HMGA2
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DOI：
10.4161/cc.6.21.4845
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发表时间：
2007-11-01
期刊：
影响因子：
4.3
通讯作者：
Peter, Marcus E.
中科院分区：
文献类型：
--
作者：
Park, Sun-Mi;Shell, Scott;Peter, Marcus E.
微小RNA let - 7通过抑制一些基因（如c - myc和RAS以及胚胎基因高迁移率族A2（HMGA2））的表达来调控胚胎晚期发育。我们现在证明，let - 7对HMGA2的靶向作用比对RAS更有效。在NCI60细胞系中，其表达与let - 7的表达呈负相关，并且当将能有效沉默HMGA2表达的let - 7量引入肿瘤细胞时，RAS的表达没有变化。我们没有发现原发性卵巢癌样本和匹配的转移瘤之间HMGA2的表达存在差异，这表明HMGA2的表达代表了癌症进展过程中的一个早期事件。在胚胎发育过程中let - 7对HMGA2的晚期抑制，以及在癌症发展过程中HMGA2的早期重新表达，与癌症发展代表一种反向胚胎发生的假说相符。
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.