机构：[1]State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China[2]Advanced Medical Research Institute, Shandong University, Jinan, China[3]School of Biological Science and Technology, University of Jinan, Jinan, China[4]Biomedical Translational Research Institute, Jinan University, Guangzhou, Guangdong, China[5]School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China[6]Tianjin Key Laboratory of human development and reproductive regulation, Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin, China[7]Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China河北医科大学第四医院[8]The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan, Guangdong, China[9]Department of Colorectal Surgery, Tianjin Union Medical Center, Nankai University, Tianjin, China[10]Department of Pathology, Medical School, Dalian University, Dalian, Liaoning, China[11]State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
Protein arginine methyltransferase 5 (PRMT5) is a major type II enzyme responsible for symmetric dimethylation of arginine (SDMA), and plays predominantly roles in human cancers, including in ovarian cancer. However, the exactly roles and underlying mechanisms of PRMT5 contributing to the progression of ovarian cancer mediated by reprogramming cell metabolism remain largely elusive. Here, we report that PRMT5 is highly expressed and correlates with poor survival in ovarian cancer. Knockdown or pharmaceutical inhibition of PRMT5 is sufficient to decrease glycolysis flux, attenuate tumor growth, and enhance the antitumor effect of Taxol. Mechanistically, we find that PRMT5 symmetrically dimethylates alpha-enolase (ENO1) at arginine 9 to promotes active ENO1 dimer formation, which increases glycolysis flux and accelerates tumor growth. Moreover, PRMT5 signals high glucose to increase the methylation modification of ENO1. Together, our data reveal a novel role of PRMT5 in promoting ovarian cancer growth by controlling glycolysis flux mediated by methylating ENO1, and highlights that PRMT5 may represent a promising therapeutic target for treating ovarian cancer.
基金：
National Natural Science Foundation of China [81973356, 82273963]; Natural Science Foundation of Tianjin [21JCZDJC00060]; Tianjin Key Laboratory of human development and reproductive regulation [2020XHY02]; Tianjin Key Medical Discipline (Specialty) Construction Project [TJYXZDXK-043A]
第一作者机构：[1]State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China
共同第一作者：
通讯作者：
通讯机构：[1]State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China[5]School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China[6]Tianjin Key Laboratory of human development and reproductive regulation, Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin, China[11]State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China[*1]State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China.[*2]School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.[*3]State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.[*4]Tianjin Key Laboratory of human development and reproductive regulation, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin 300100, China.
推荐引用方式(GB/T 7714)：
Xie Fei,Zhang Han,Zhu Kongkai,et al.PRMT5 promotes ovarian cancer growth through enhancing Warburg effect by methylating ENO1[J].MEDCOMM.2023,4(2):doi:10.1002/mco2.245.
APA：
Xie, Fei,Zhang, Han,Zhu, Kongkai,Jiang, Cheng-Shi,Zhang, Xiaoya...&Shan, Changliang.(2023).PRMT5 promotes ovarian cancer growth through enhancing Warburg effect by methylating ENO1.MEDCOMM,4,(2)
MLA：
Xie, Fei,et al."PRMT5 promotes ovarian cancer growth through enhancing Warburg effect by methylating ENO1".MEDCOMM 4..2(2023)
医学