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PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism
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, tumo...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9939295/ https://www.ncbi.nlm.nih.gov/pubmed/36815049 http://dx.doi.org/10.1016/j.apsb.2022.05.019 |
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author | Sun, Mingming Li, Leilei Niu, Yujia Wang, Yingzhi Yan, Qi Xie, Fei Qiao, Yaya Song, Jiaqi Sun, Huanran Li, Zhen Lai, Sizhen Chang, Hongkai Zhang, Han Wang, Jiyan Yang, Chenxin Zhao, Huifang Tan, Junzhen Li, Yanping Liu, Shuangping Lu, Bin Liu, Min Kong, Guangyao Zhao, Yujun Zhang, Chunze Lin, Shu-Hai Luo, Cheng Zhang, Shuai Shan, Changliang |
author_facet | Sun, Mingming Li, Leilei Niu, Yujia Wang, Yingzhi Yan, Qi Xie, Fei Qiao, Yaya Song, Jiaqi Sun, Huanran Li, Zhen Lai, Sizhen Chang, Hongkai Zhang, Han Wang, Jiyan Yang, Chenxin Zhao, Huifang Tan, Junzhen Li, Yanping Liu, Shuangping Lu, Bin Liu, Min Kong, Guangyao Zhao, Yujun Zhang, Chunze Lin, Shu-Hai Luo, Cheng Zhang, Shuai Shan, Changliang |
author_sort | Sun, Mingming |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9939295 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-99392952023-02-21 PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism Sun, Mingming Li, Leilei Niu, Yujia Wang, Yingzhi Yan, Qi Xie, Fei Qiao, Yaya Song, Jiaqi Sun, Huanran Li, Zhen Lai, Sizhen Chang, Hongkai Zhang, Han Wang, Jiyan Yang, Chenxin Zhao, Huifang Tan, Junzhen Li, Yanping Liu, Shuangping Lu, Bin Liu, Min Kong, Guangyao Zhao, Yujun Zhang, Chunze Lin, Shu-Hai Luo, Cheng Zhang, Shuai Shan, Changliang Acta Pharm Sin B Original Article 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. Elsevier 2023-01 2022-05-25 /pmc/articles/PMC9939295/ /pubmed/36815049 http://dx.doi.org/10.1016/j.apsb.2022.05.019 Text en © 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Sun, Mingming Li, Leilei Niu, Yujia Wang, Yingzhi Yan, Qi Xie, Fei Qiao, Yaya Song, Jiaqi Sun, Huanran Li, Zhen Lai, Sizhen Chang, Hongkai Zhang, Han Wang, Jiyan Yang, Chenxin Zhao, Huifang Tan, Junzhen Li, Yanping Liu, Shuangping Lu, Bin Liu, Min Kong, Guangyao Zhao, Yujun Zhang, Chunze Lin, Shu-Hai Luo, Cheng Zhang, Shuai Shan, Changliang PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism |
title | PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism |
title_full | PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism |
title_fullStr | PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism |
title_full_unstemmed | PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism |
title_short | PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism |
title_sort | prmt6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6pgd/eno1 mediated cell metabolism |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9939295/ https://www.ncbi.nlm.nih.gov/pubmed/36815049 http://dx.doi.org/10.1016/j.apsb.2022.05.019 |
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