PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism.
PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism.
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PRMT6通过触发6PGD/ENO1介导的细胞代谢促进肺癌的致瘤性和顺铂反应
DOI：
10.1016/j.apsb.2022.05.019
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发表时间：
2023-01
影响因子：
14.5
通讯作者：
Shan, Changliang
中科院分区：
文献类型：
--
作者：
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
关键词：
代谢重编程是包括肺癌在内的癌症的一个标志。然而，确切的潜在机制和治疗潜力在很大程度上尚不清楚。在此，我们报道了精氨酸甲基转移酶6(PRMT6)蛋白在肺癌中的高表达，并且在肺癌的细胞代谢、致瘤性和顺铂反应中是必需的。PRMT6通过增加6-磷酸葡萄糖酸脱氢酶(6PGD)和α-烯醇化酶(ENO1)的活性，调节人肺癌细胞中氧化戊糖磷酸途径的通量和糖酵解途径。此外，PRMT6甲基化6PGD的R324以提高其活性，而ENO1的R9和R372甲基化分别促进活性ENO1二聚体的形成和2-磷酸甘油(2-PG)与ENO1的结合。最后，靶向PRMT6阻断了氧化PPP通量、糖酵解途径和肿瘤生长，并增强了顺铂对肺癌的抗肿瘤作用。综上所述，本研究表明PRMT6作为糖代谢的翻译后修饰(PTM)调节因子，导致肺癌的发生。已有研究证明，PRMT6-6PGD/ENO1调节轴是肿瘤发生的重要决定因素，可能成为一种有前途的肿瘤治疗策略。PRMT6通过调节6PGD/ENO1的不对称精氨酸脱甲基化修饰，增强氧化戊糖磷酸途径通量和糖酵解途径，从而促进肺癌生长和顺铂反应。
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. PRMT6 promotes lung cancer growth and cisplatin response through enhancing oxidative pentose phosphate pathway flux and glycolysis pathway, which mediated by regulating the asymmetric arginine demethylation modification of 6PGD/ENO1.
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影响因子：
16.6
作者：
Yamamoto, Takehiro;Takano, Naoharu;Ishiwata, Kyoko;Ohmura, Mitsuyo;Nagahata, Yoshiko;Matsuura, Tomomi;Kamata, Aki;Sakamoto, Kyoko;Nakanishi, Tsuyoshi;Kubo, Akiko;Hishiki, Takako;Suematsu, Makoto
通讯作者：
Suematsu, Makoto
影响因子：
13.5
作者：
Wong, Tin-Lok;Ng, Kai-Yu;Ma, Stephanie
通讯作者：
Ma, Stephanie
影响因子：
14.5
作者：
Zhang, Zhiwei;Ding, Suling;Wang, Zhe;Zhu, Xiaowei;Zhou, Zheliang;Zhang, Weiwei;Yang, Xiangdong;Ge, Junbo
通讯作者：
Ge, Junbo
DOI：
10.1016/j.apsb.2021.09.019
发表时间：
2022-03
期刊：
Acta pharmaceutica Sinica. B
影响因子：
--
作者：
Du D;Liu C;Qin M;Zhang X;Xi T;Yuan S;Hao H;Xiong J
通讯作者：
Xiong J
影响因子：
28.2
作者：
Kitajima S;Ivanova E;Guo S;Yoshida R;Campisi M;Sundararaman SK;Tange S;Mitsuishi Y;Thai TC;Masuda S;Piel BP;Sholl LM;Kirschmeier PT;Paweletz CP;Watanabe H;Yajima M;Barbie DA
通讯作者：
Barbie DA