Yang W, Du W W, Li X, Yee A J, Yang B B
Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Oncogene. 2016 Jul 28;35(30):3919-31. doi: 10.1038/onc.2015.460. Epub 2015 Dec 14.
It has recently been shown that the upregulation of a pseudogene specific to a protein-coding gene could function as a sponge to bind multiple potential targeting microRNAs (miRNAs), resulting in increased gene expression. Similarly, it was recently demonstrated that circular RNAs can function as sponges for miRNAs, and could upregulate expression of mRNAs containing an identical sequence. Furthermore, some mRNAs are now known to not only translate protein, but also function to sponge miRNA binding, facilitating gene expression. Collectively, these appear to be effective mechanisms to ensure gene expression and protein activity. Here we show that expression of a member of the forkhead family of transcription factors, Foxo3, is regulated by the Foxo3 pseudogene (Foxo3P), and Foxo3 circular RNA, both of which bind to eight miRNAs. We found that the ectopic expression of the Foxo3P, Foxo3 circular RNA and Foxo3 mRNA could all suppress tumor growth and cancer cell proliferation and survival. Our results showed that at least three mechanisms are used to ensure protein translation of Foxo3, which reflects an essential role of Foxo3 and its corresponding non-coding RNAs.
最近研究表明，蛋白质编码基因特异的假基因上调可作为海绵结合多个潜在靶向微小RNA（miRNA），从而导致基因表达增加。类似地，最近有研究证明环状RNA可作为miRNA的海绵，并能上调含有相同序列的mRNA的表达。此外，现在已知一些mRNA不仅能翻译蛋白质，还具有结合miRNA的海绵功能，促进基因表达。总体而言，这些似乎是确保基因表达和蛋白质活性的有效机制。在此我们表明，转录因子叉头家族成员Foxo3的表达受Foxo3假基因（Foxo3P）和Foxo3环状RNA调控，二者均可结合8种miRNA。我们发现，Foxo3P、Foxo3环状RNA和Foxo3 mRNA的异位表达均能抑制肿瘤生长以及癌细胞的增殖和存活。我们的结果表明，至少有三种机制用于确保Foxo3的蛋白质翻译，这反映了Foxo3及其相应非编码RNA的重要作用。
