The let-7 MicroRNA represses cell proliferation pathways in human cells
The let-7 MicroRNA represses cell proliferation pathways in human cells
复制标题
DOI：
10.1158/0008-5472.can-07-1083
复制
发表时间：
2007-08-15
期刊：
影响因子：
11.2
通讯作者：
Slack, Frank J.
中科院分区：
文献类型：
--
作者：
Johnson, Charles D.;Esquela-Kerscher, Aurora;Slack, Frank J.
microRNA在动物发育、细胞分化和代谢中起重要作用，并与人类癌症有关。let-7 microRNA控制秀丽隐杆线虫细胞周期退出和终末分化的时间，在人类肺肿瘤中表达不足或缺失。在这里，我们发现let-7在正常肺组织中高度表达，并且抑制let-7功能会导致A549肺癌细胞的细胞分裂增加。let-7在癌细胞系中的过表达改变了细胞周期进程并减少了细胞分裂，这为let-7在肺细胞中作为肿瘤抑制因子发挥作用提供了证据。let-7以前被证明可以调节RAS肺癌癌基因的表达，我们的工作现在表明，参与细胞周期和细胞分裂功能的多个基因也直接或间接地被let-7抑制。这项工作揭示了let-7 microRNA是细胞增殖途径的主要调节因子。
MicroRNAs play important roles in animal development, cell differentiation, and metabolism and have been implicated in human cancer. The let-7 microRNA controls the timing of cell cycle exit and terminal differentiation in Caenorhabditis elegans and is poorly expressed or deleted in human lung tumors. Here, we show that let-7 is highly expressed in normal lung tissue, and that inhibiting let-7 function leads to increased cell division in A549 lung cancer cells. Overexpression of let-7 in cancer cell lines alters cell cycle progression and reduces cell division, providing evidence that let-7 functions as a tumor suppressor in lung cells. let-7 was previously shown to regulate the expression of the RAS lung cancer oncogenes, and our work now shows that multiple genes involved in cell cycle and cell division functions are also directly or indirectly repressed by let-7. This work reveals the let-7 microRNA to be a master regulator of cell proliferation pathways.