Laboratory of Cancer Biology Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, UK.
Argonaut Therapeutics Ltd Magdalen Centre, Oxford Science Park, Oxford, OX4 4GA, UK.
Cell Death Dis. 2020 Jul 24;11(7):572. doi: 10.1038/s41419-020-02771-9.
The pRb-E2F pathway is a critical point of regulation in the cell cycle and loss of control of the pathway is a hallmark of cancer. E2F1 is the major target through which pRb exerts its effects and arginine methylation by PRMT5 plays a key role in dictating E2F1 activity. Here we have explored the functional role of the PRMT5-E2F1 axis and highlight its influence on different aspects of cancer cell biology including viability, migration, invasion and adherence. Through a genome-wide expression analysis, we identified a distinct set of genes under the control of PRMT5 and E2F1, including some highly regulated genes, which influence cell migration, invasio and adherence through a PRMT5-dependent mechanism. Most significantly, a coincidence was apparent between the expression of PRMT5 and E2F1 in human tumours, and elevated levels of PRMT5 and E2F1 correlated with poor prognosis disease. Our results suggest a causal relationship between PRMT5 and E2F1 in driving the malignant phenotype and thereby highlight an important pathway for therapeutic intervention.
pRb-E2F 通路是细胞周期调控的关键点，该通路的失控是癌症的一个标志。E2F1 是 pRb 发挥作用的主要靶点，而 PRMT5 介导的精氨酸甲基化在决定 E2F1 活性方面起着关键作用。在这里，我们探讨了 PRMT5-E2F1 轴的功能作用，并强调了它对癌细胞生物学不同方面的影响，包括活力、迁移、侵袭和黏附。通过全基因组表达分析，我们确定了一组受 PRMT5 和 E2F1 控制的独特基因，其中包括一些高度调控的基因，这些基因通过 PRMT5 依赖的机制影响细胞迁移、侵袭和黏附。最重要的是，在人类肿瘤中，PRMT5 和 E2F1 的表达明显一致，PRMT5 和 E2F1 的水平升高与预后不良的疾病相关。我们的研究结果表明，PRMT5 和 E2F1 之间存在因果关系，导致恶性表型，从而突出了一个重要的治疗干预途径。
