PRMT5 promotes ovarian cancer growth through enhancing Warburg effect by methylating ENO1
Fei Xie,
Han Zhang,
Kongkai Zhu,
Cheng‐Shi Jiang,
Xiaoya Zhang,
Hongkai Chang,
Yaya Qiao,
Mingming Sun,
Jiyan Wang,
Mukuo Wang,
Junzhen Tan,
Tao Wang,
Lianmei Zhao,
Yuan Zhang,
Jianping Lin,
Chunze Zhang,
Shuangping Liu,
Jianguo Zhao,
Cheng Luo,
Shuai Zhang,
Changliang Shan
Affiliations
Fei Xie
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research Nankai University Tianjin China
Han Zhang
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research Nankai University Tianjin China
Kongkai Zhu
Advanced Medical Research Institute Shandong University Jinan China
Cheng‐Shi Jiang
School of Biological Science and Technology University of Jinan Jinan China
Xiaoya Zhang
Biomedical Translational Research Institute Jinan University Guangzhou Guangdong China
Hongkai Chang
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research Nankai University Tianjin China
Yaya Qiao
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research Nankai University Tianjin China
Mingming Sun
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research Nankai University Tianjin China
Jiyan Wang
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research Nankai University Tianjin China
Mukuo Wang
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research Nankai University Tianjin China
Junzhen Tan
School of Integrative Medicine Tianjin University of Traditional Chinese Medicine Tianjin China
Tao Wang
Tianjin Key Laboratory of human development and reproductive regulation Tianjin Central Hospital of Obstetrics and Gynecology Tianjin China
Lianmei Zhao
Research Center The Fourth Hospital of Hebei Medical University Shijiazhuang Hebei China
Yuan Zhang
The Sixth Affiliated Hospital of Guangzhou Medical University Qingyuan Guangdong China
Jianping Lin
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research Nankai University Tianjin China
Chunze Zhang
Department of Colorectal Surgery, Tianjin Union Medical Center Nankai University Tianjin China
Shuangping Liu
Department of Pathology, Medical School Dalian University Dalian Liaoning China
Jianguo Zhao
Tianjin Key Laboratory of human development and reproductive regulation Tianjin Central Hospital of Obstetrics and Gynecology Tianjin China
Cheng Luo
State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China
Shuai Zhang
School of Integrative Medicine Tianjin University of Traditional Chinese Medicine Tianjin China
Changliang Shan
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research Nankai University Tianjin China
Abstract 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.
