Yuanyang Yuan1, Hong Nie2. 1. Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, China. 2. Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, China. hine@sjtu.edu.cn.
Abstract
BACKGROUND: PRMT5 is a type II protein arginine methyltransferase that methylates histone or non-histone proteins. Arginine methylation by PRMT5 has been implicated in gene transcription, ribosome biogenesis, RNA transport, pre-mRNA splicing and signal transduction. High expression of PRMT5 has been observed in various cancers and PRMT5 overexpression has been reported to improve cancer cell survival, proliferation, migration and metabolism and to inhibit cancer cell apoptosis. In addition, PRMT5 has been found to be required for cancer stem cell survival, self-renewal and differentiation. Several microRNAs have been shown to regulate PRMT5 expression. As PRMT5 has oncogene-like properties, several PRMT5 inhibitors have been used to explore their efficacy as potential drugs for different types of cancer, and three of them are now being tested in clinical trials. CONCLUSIONS: In this review, we summarize current knowledge on the role of PRMT5 in cancer development and progression, including its functions and underlying mechanisms. In addition, we highlight the rapid development of PRMT5 inhibitors and summarize ongoing clinical trials for cancer therapy. By affecting both tumor cells and the tumor microenvironment, PRMT5 inhibitors may serve as effective anti-cancer agents, especially when combined with immune therapies.
BACKGROUND:PRMT5 is a type II protein arginine methyltransferase that methylates histone or non-histone proteins. Arginine methylation by PRMT5 has been implicated in gene transcription, ribosome biogenesis, RNA transport, pre-mRNA splicing and signal transduction. High expression of PRMT5 has been observed in various cancers and PRMT5 overexpression has been reported to improve cancer cell survival, proliferation, migration and metabolism and to inhibit cancer cell apoptosis. In addition, PRMT5 has been found to be required for cancer stem cell survival, self-renewal and differentiation. Several microRNAs have been shown to regulate PRMT5 expression. As PRMT5 has oncogene-like properties, several PRMT5 inhibitors have been used to explore their efficacy as potential drugs for different types of cancer, and three of them are now being tested in clinical trials. CONCLUSIONS: In this review, we summarize current knowledge on the role of PRMT5 in cancer development and progression, including its functions and underlying mechanisms. In addition, we highlight the rapid development of PRMT5 inhibitors and summarize ongoing clinical trials for cancer therapy. By affecting both tumor cells and the tumor microenvironment, PRMT5 inhibitors may serve as effective anti-cancer agents, especially when combined with immune therapies.
Authors: Stephen Antonysamy; Zahid Bonday; Robert M Campbell; Brandon Doyle; Zhanna Druzina; Tarun Gheyi; Bomie Han; Louis N Jungheim; Yuewei Qian; Charles Rauch; Marijane Russell; J Michael Sauder; Stephen R Wasserman; Kenneth Weichert; Francis S Willard; Aiping Zhang; Spencer Emtage Journal: Proc Natl Acad Sci U S A Date: 2012-10-15 Impact factor: 11.205
Authors: Meng-Chiao Ho; Carola Wilczek; Jeffrey B Bonanno; Li Xing; Janina Seznec; Tsutomu Matsui; Lester G Carter; Takashi Onikubo; P Rajesh Kumar; Man K Chan; Michael Brenowitz; R Holland Cheng; Ulf Reimer; Steven C Almo; David Shechter Journal: PLoS One Date: 2013-02-25 Impact factor: 3.240