Targeting methyltransferase PRMT5 retards the carcinogenesis and metastasis of HNSCC via epigenetically inhibiting Twist1 transcription.
Targeting methyltransferase PRMT5 retards the carcinogenesis and metastasis of HNSCC via epigenetically inhibiting Twist1 transcription.
复制标题
靶向甲基转移酶 PRMT5 通过表观遗传学抑制 Twist1 转录来延缓 HNSCC 的癌变和转移
DOI：
10.1016/j.neo.2020.09.004
复制
发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
Xia J
中科院分区：
文献类型：
--
作者：
Fan Z;He L;Li M;Cao R;Deng M;Ping F;Liang X;He Y;Wu T;Tao X;Xu J;Cheng B;Xia J
Protein arginine methyltransferase 5 (PRMT5) is an important type II arginine methyltransferase that can play roles in cancers in a highly tissue-specific manner, but its role in the carcinogenesis and metastasis of head and neck squamous cell carcinoma (HNSCC) remains unclear. Here, we detected PRMT5 expression in HNSCC tissues and performed series of in vivo and in vitro assays to investigate the function and mechanism of PRMT5 in HNSCC. We found that PRMT5 was overexpressed in dysplastic and cancer tissues, and associated with lymph node metastasis and worse patient survival. PRMT5 knockdown repressed the malignant phenotype of HNSCC cells in vitro and in vivo. PRMT5 specific inhibitor blocked the formation of precancerous lesion and HNSCC in 4NQO-induced tongue carcinogenesis model, prevented lymph node metastasis in tongue orthotopic xenograft model and inhibited cancer development in subcutaneous xenograft model and Patient-Derived tumor Xenograft (PDX) model. Mechanistically, PRMT5-catalyzed H3R2me2s promotes the enrichment of H3K4me3 in the Twist1 promoter region by recruiting WDR5, and subsequently activates the transcription of Twist1. The rescue experiments indicated that overexpressed Twist1 abrogated the inhibition of cell invasion induced by PRMT5 inhibitor. In summary, this study elucidates that PRMT5 inhibition could reduce H3K4me3-mediated Twist1 transcription and retard the carcinogenesis and metastasis of HNSCC.
登录
查看更多内容
影响因子：
8.8
作者：
Chiang K;Zielinska AE;Shaaban AM;Sanchez-Bailon MP;Jarrold J;Clarke TL;Zhang J;Francis A;Jones LJ;Smith S;Barbash O;Guccione E;Farnie G;Smalley MJ;Davies CC
通讯作者：
Davies CC
影响因子：
11.2
作者：
Malek R;Gajula RP;Williams RD;Nghiem B;Simons BW;Nugent K;Wang H;Taparra K;Lemtiri-Chlieh G;Yoon AR;True L;An SS;DeWeese TL;Ross AE;Schaeffer EM;Pienta KJ;Hurley PJ;Morrissey C;Tran PT
通讯作者：
Tran PT
MLL家族甲基转移酶活性调节的结构基础
影响因子：
64.8
作者：
Li, Yanjing;Han, Jianming;Zhang, Yuebin;Cao, Fang;Liu, Zhijun;Li, Shuai;Wu, Jian;Hu, Chunyi;Wang, Yan;Shuai, Jin;Chen, Juan;Cao, Liaoran;Li, Dangsheng;Shi, Pan;Tian, Changlin;Zhang, Jian;Dou, Yali;Li, Guohui;Chen, Yong;Lei, Ming
通讯作者：
Lei, Ming
影响因子：
8.9
作者：
Marur, Shanthi;Forastiere, Arlene A.
通讯作者：
Forastiere, Arlene A.
影响因子：
23.9
作者：
Beck, Benjamin;Lapouge, Gaelle;Blanpain, Cedric
通讯作者：
Blanpain, Cedric