Cancer Genetics Program, Department of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Proc Natl Acad Sci U S A. 2013 Apr 30;110(18):7154-9. doi: 10.1073/pnas.1222509110. Epub 2013 Mar 27.
Competitive endogenous (ce)RNAs cross-regulate each other through sequestration of shared microRNAs and form complex regulatory networks based on their microRNA signature. However, the molecular requirements for ceRNA cross-regulation and the extent of ceRNA networks remain unknown. Here, we present a mathematical mass-action model to determine the optimal conditions for ceRNA activity in silico. This model was validated using phosphatase and tensin homolog (PTEN) and its ceRNA VAMP (vesicle-associated membrane protein)-associated protein A (VAPA) as paradigmatic examples. A computational assessment of the complexity of ceRNA networks revealed that transcription factor and ceRNA networks are intimately intertwined. Notably, we found that ceRNA networks are responsive to transcription factor up-regulation or their aberrant expression in cancer. Thus, given optimal molecular conditions, alterations of one ceRNA can have striking effects on integrated ceRNA and transcriptional networks.
竞争性内源性 (ce)RNAs 通过共享 microRNAs 的隔离相互调控，并根据其 microRNA 特征形成复杂的调控网络。然而，ceRNA 交叉调控的分子要求以及 ceRNA 网络的范围尚不清楚。在这里，我们提出了一种数学质量作用模型，以确定 ceRNA 活性的最佳条件。该模型使用磷酸酶和张力蛋白同源物 (PTEN) 及其 ceRNA VAMP（囊泡相关膜蛋白）相关蛋白 A (VAPA) 作为典范示例进行了验证。对 ceRNA 网络复杂性的计算评估表明，转录因子和 ceRNA 网络紧密交织。值得注意的是，我们发现 ceRNA 网络对转录因子的上调或其在癌症中的异常表达敏感。因此，在最佳分子条件下，一个 ceRNA 的改变会对整合的 ceRNA 和转录网络产生显著影响。
