Acta Pharmaceutica Sinica B (Jan 2023)
PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism
- Mingming Sun,
- Leilei Li,
- Yujia Niu,
- Yingzhi Wang,
- Qi Yan,
- Fei Xie,
- Yaya Qiao,
- Jiaqi Song,
- Huanran Sun,
- Zhen Li,
- Sizhen Lai,
- Hongkai Chang,
- Han Zhang,
- Jiyan Wang,
- Chenxin Yang,
- Huifang Zhao,
- Junzhen Tan,
- Yanping Li,
- Shuangping Liu,
- Bin Lu,
- Min Liu,
- Guangyao Kong,
- Yujun Zhao,
- Chunze Zhang,
- Shu-Hai Lin,
- Cheng Luo,
- Shuai Zhang,
- Changliang Shan
Affiliations
- Mingming Sun
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China
- Leilei Li
- Biomedical Translational Research Institute, Jinan University, Guangzhou 510632, China
- Yujia Niu
- State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, China
- Yingzhi Wang
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China
- Qi Yan
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China
- Fei Xie
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China
- Yaya Qiao
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China
- Jiaqi Song
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China
- Huanran Sun
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China
- Zhen Li
- Biomedical Translational Research Institute, Jinan University, Guangzhou 510632, China
- Sizhen Lai
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
- Hongkai Chang
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China
- Han Zhang
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China
- Jiyan Wang
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China
- Chenxin Yang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
- Huifang Zhao
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
- Junzhen Tan
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
- Yanping Li
- Department of Pathology and Institute of Precision Medicine, Jining Medical University, Jining 272067, China
- Shuangping Liu
- Department of Pathology, Medical School, Dalian University, Dalian 116622, China
- Bin Lu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang 421001, China; School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China
- Min Liu
- Institute of Biomedical Sciences, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, College of Life Sciences, Shandong Normal University, Jinan 250014, China
- Guangyao Kong
- National Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
- Yujun Zhao
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- Chunze Zhang
- Department of Colorectal Surgery, Tianjin Union Medical Center, Nankai University, Tianjin 300121, China
- Shu-Hai Lin
- State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, China; Corresponding authors.
- Cheng Luo
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Corresponding authors.
- Shuai Zhang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Corresponding authors.
- Changliang Shan
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Corresponding authors.
- Journal volume & issue
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Vol. 13,
no. 1
pp. 157 – 173
Abstract
Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.
