PRMT5 Promotes Human Lung Cancer Cell Apoptosis via Akt/Gsk3β Signaling Induced by Resveratrol

Cell Transplantation

Original Articles

Yiwen Long¹  Yong Li²  Xiaoping Liu³  Yanxia Yang⁴  Yonghua Zheng⁵ 

[1] Department of Critical Care Medicine, Luwan Branch of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China;Department of Respiratory Medicine, Luwan Branch of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China;Both the authors contributed equally to this article;Department of Respiratory Medicine, Second People’s Hospital of Gansu Province & Northwest Minzu University Affiliated Hospital, Lanzhou, China;Department of Respiratory Medicine, Second People’s Hospital of Gansu Province & Northwest Minzu University Affiliated Hospital, Lanzhou, China;Both the authors contributed equally to this article;Department of Respiratory Medicine, Shanghai Jinshan Tinglin Hospital, Shanghai, China;

关键词: PRMT5;    Akt;    GSK3β;    cyclin D1;    cyclin E1;    lung cancer;    resveratrol;   

DOI  :  10.1177/0963689719885083

 received in 2019-08-19, accepted in 2019-10-06,  发布年份 2019

来源: Sage Journals

【 摘 要 】

Protein arginine methyltransferase 5 (PRMT5) is implicated in various types of human cancer and tumor development, especially in lung cancer. Nevertheless, it is still unclear whether suppression of PRMT5 could promote lung cancer cell apoptosis and chemosensitivity induced by resveratrol, and the underlying molecular mechanism remains completely unknown. Here, we showed that PRMT5 was overexpressed in human lung cancer tissues and different types of lung cancer cell lines. Moreover, we constructed PRMT5 stable knockdown cell lines (A549 and ASCT-a-1) and investigated the roles of PRMT5 and the related signaling pathway in lung cancer cell apoptosis induced by resveratrol. Our results indicated that inhibition or down-regulation of PRMT5 by GSK591, a PRMT5-specific inhibitor, or shRNAs markedly enhanced cell apoptosis and chemosensitivity stimulated by resveratrol. Further investigation showed that inhibition or down-regulation of PRMT5 further reduced Akt/GSK3β phosphorylation and the downstream targets cyclin D1 and E1 expression upon resveratrol treatment. Our findings suggest that PRMT5 is a pivotal mediator for human lung cancer cell death induced by resveratrol, which also reveals that PRMT5 may serve as a new therapeutic target for the treatment of human lung cancer.

【 授权许可】

CC BY-NC   
© The Author(s) 2019

【 图 表 】

Figure 1.

Figure 8.