The ERK1/2 (RAS, RAF, MEK, ERK) and PI3K (PI3K, AKT, mTOR, PTEN) pathways are the chief signaling pathways for cellular proliferation, survival, and differentiation. Overactivation and hyperphosphorylation of the ERK1/2 & PI3K pathways is frequently observed in cancer and is associated with poor patient prognosis. While it is well known that genetic alterations lead to the dysregulation of the ERK1/2 & PI3K pathways, increasing evidence is showcasing that epigenetic alterations also play a major role in the regulation of the ERK1/2 & PI3K pathways. Protein Arginine Methyltransferase 5 (PRMT5) is a post-translational modifier for multiple cellular processes that is currently being tested as a therapeutic target for cancer. PRMT5 has been shown to be overexpressed in many types of cancers, as well as negatively correlated with patient survival. Numerous studies are indicating that as a post-translational modifier, PRMT5 is extensively involved in regulating the ERK1/2 & PI3K pathways. Additionally, a large number of in vitro and in vivo studies are demonstrating that PRMT5 inhibition, as well as PRMT5 and ERK1/2 & PI3K combination therapies, show significant therapeutic effects in many cancer types. In this review, we explore the vast interactions that PRMT5 has with the ERK1/2 & PI3K pathways, and we make the case for further testing of PRMT5 inhibition, as well as PRMT5 and ERK1/2 & PI3K combination therapies, for the treatment of cancer.

中文翻译：

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蛋白质精氨酸甲基转移酶 5 (PRMT5) 和 ERK1/2 和 PI3K 通路：PRMT5 抑制和联合治疗癌症的案例

ERK1/2（RAS、RAF、MEK、ERK）和 PI3K（PI3K、AKT、mTOR、PTEN）通路是细胞增殖、存活和分化的主要信号通路。在癌症中经常观察到 ERK1/2 和 PI3K 通路的过度激活和过度磷酸化，并且与患者预后不良有关。虽然众所周知遗传改变会导致 ERK1/2 和 PI3K 通路的失调，但越来越多的证据表明，表观遗传改变也在 ERK1/2 和 PI3K 通路的调节中发挥重要作用。蛋白质精氨酸甲基转移酶 5 (PRMT5) 是多种细胞过程的翻译后修饰剂，目前正在作为癌症治疗靶点进行测试。PRMT5 已被证明在多种癌症中过度表达，并且与患者生存呈负相关。大量研究表明，作为翻译后修饰剂，PRMT5 广泛参与调节 ERK1/2 和 PI3K 通路。此外，大量体外和体内研究表明，PRMT5 抑制以及 PRMT5 和 ERK1/2 和 PI3K 联合疗法在许多癌症类型中显示出显着的治疗效果。在这篇综述中，我们探讨了 PRMT5 与 ERK1/2 和 PI3K 通路之间的广泛相互作用，并为进一步测试 PRMT5 抑制以及 PRMT5 和 ERK1/2 和 PI3K 联合疗法以治疗癌症。大量体外和体内研究表明，PRMT5 抑制以及 PRMT5 和 ERK1/2 和 PI3K 联合疗法在许多癌症类型中显示出显着的治疗效果。在这篇综述中，我们探讨了 PRMT5 与 ERK1/2 和 PI3K 通路之间的广泛相互作用，并为进一步测试 PRMT5 抑制以及 PRMT5 和 ERK1/2 和 PI3K 联合疗法以治疗癌症。大量体外和体内研究表明，PRMT5 抑制以及 PRMT5 和 ERK1/2 和 PI3K 联合疗法在许多癌症类型中显示出显着的治疗效果。在这篇综述中，我们探讨了 PRMT5 与 ERK1/2 和 PI3K 通路之间的广泛相互作用，并为进一步测试 PRMT5 抑制以及 PRMT5 和 ERK1/2 和 PI3K 联合疗法以治疗癌症。