PRMT5 promotes ovarian cancer growth through enhancing Warburg effect by methylating ENO1
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 p...
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| Format: | Article |
| Language: | English |
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Wiley
2023-04-01
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| Series: | MedComm |
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| Online Access: | https://doi.org/10.1002/mco2.245 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Fei Xie |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-8c1a0d509b124df5ae4a85577bce88bb |
| institution | Kabale University |
| issn | 2688-2663 |
| language | English |
| publishDate | 2023-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj-art-8c1a0d509b124df5ae4a85577bce88bb2025-01-24T05:36:29ZengWileyMedComm2688-26632023-04-0142n/an/a10.1002/mco2.245PRMT5 promotes ovarian cancer growth through enhancing Warburg effect by methylating ENO1Fei Xie0Han Zhang1Kongkai Zhu2Cheng‐Shi Jiang3Xiaoya Zhang4Hongkai Chang5Yaya Qiao6Mingming Sun7Jiyan Wang8Mukuo Wang9Junzhen Tan10Tao Wang11Lianmei Zhao12Yuan Zhang13Jianping Lin14Chunze Zhang15Shuangping Liu16Jianguo Zhao17Cheng Luo18Shuai Zhang19Changliang Shan20State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research Nankai University Tianjin ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research Nankai University Tianjin ChinaAdvanced Medical Research Institute Shandong University Jinan ChinaSchool of Biological Science and Technology University of Jinan Jinan ChinaBiomedical Translational Research Institute Jinan University Guangzhou Guangdong ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research Nankai University Tianjin ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research Nankai University Tianjin ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research Nankai University Tianjin ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research Nankai University Tianjin ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research Nankai University Tianjin ChinaSchool of Integrative Medicine Tianjin University of Traditional Chinese Medicine Tianjin ChinaTianjin Key Laboratory of human development and reproductive regulation Tianjin Central Hospital of Obstetrics and Gynecology Tianjin ChinaResearch Center The Fourth Hospital of Hebei Medical University Shijiazhuang Hebei ChinaThe Sixth Affiliated Hospital of Guangzhou Medical University Qingyuan Guangdong ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research Nankai University Tianjin ChinaDepartment of Colorectal Surgery, Tianjin Union Medical Center Nankai University Tianjin ChinaDepartment of Pathology, Medical School Dalian University Dalian Liaoning ChinaTianjin Key Laboratory of human development and reproductive regulation Tianjin Central Hospital of Obstetrics and Gynecology Tianjin ChinaState Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai ChinaSchool of Integrative Medicine Tianjin University of Traditional Chinese Medicine Tianjin ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research Nankai University Tianjin ChinaAbstract 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.https://doi.org/10.1002/mco2.245alpha‐enolase (ENO1)glycolysis fluxovarian cancerprotein arginine methyltransferase 5 (PRMT5)symmetric dimethylation of arginine (SDMA) |
| spellingShingle | 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 PRMT5 promotes ovarian cancer growth through enhancing Warburg effect by methylating ENO1 MedComm alpha‐enolase (ENO1) glycolysis flux ovarian cancer protein arginine methyltransferase 5 (PRMT5) symmetric dimethylation of arginine (SDMA) |
| title | PRMT5 promotes ovarian cancer growth through enhancing Warburg effect by methylating ENO1 |
| title_full | PRMT5 promotes ovarian cancer growth through enhancing Warburg effect by methylating ENO1 |
| title_fullStr | PRMT5 promotes ovarian cancer growth through enhancing Warburg effect by methylating ENO1 |
| title_full_unstemmed | PRMT5 promotes ovarian cancer growth through enhancing Warburg effect by methylating ENO1 |
| title_short | PRMT5 promotes ovarian cancer growth through enhancing Warburg effect by methylating ENO1 |
| title_sort | prmt5 promotes ovarian cancer growth through enhancing warburg effect by methylating eno1 |
| topic | alpha‐enolase (ENO1) glycolysis flux ovarian cancer protein arginine methyltransferase 5 (PRMT5) symmetric dimethylation of arginine (SDMA) |
| url | https://doi.org/10.1002/mco2.245 |
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