Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cancer Cell. 2012 Jun 12;21(6):848-55. doi: 10.1016/j.ccr.2012.04.037.
MicroRNAs are a class of short ~22 nucleotide RNAs predicted to regulate nearly half of all protein coding genes, including many involved in basal cellular processes and organismal development. Although a global reduction in miRNAs is commonly observed in various human tumors, complete loss has not been documented, suggesting an essential function for miRNAs in tumorigenesis. Here we present the finding that transformed or immortalized Dicer1 null somatic cells can be isolated readily in vitro, maintain the characteristics of DICER1-expressing controls and remain stably proliferative. Furthermore, Dicer1 null cells from a sarcoma cell line, though depleted of miRNAs, are competent for tumor formation. Hence, miRNA levels in cancer may be maintained in vivo by a complex stabilizing selection in the intratumoral environment.
微 RNA 是一类约 22 个核苷酸的 RNA,据预测可以调节近一半的蛋白质编码基因,包括许多参与基础细胞过程和生物发育的基因。尽管在各种人类肿瘤中普遍观察到微 RNA 的整体减少,但尚未记录到完全缺失,这表明微 RNA 在肿瘤发生中具有重要功能。在这里,我们发现体外可以很容易地分离出转化或永生化的 Dicer1 缺失体体细胞,这些细胞能保持 DICER1 表达对照的特征,并保持稳定的增殖。此外,来自肉瘤细胞系的 Dicer1 缺失细胞尽管缺乏微 RNA,但仍具有肿瘤形成的能力。因此,癌症中的 miRNA 水平可能在体内通过肿瘤内环境中的复杂稳定选择来维持。