Targeting RNA helicase DHX33 blocks Ras-driven lung tumorigenesis in vivo

Wang, Xingshun1,2; Feng, Weimin1; Peng, Cheng1,2; Chen, Shiyun1; Ji, Hongbin3,4,5,6; Zhong, Hanbing1; Ge, Wei2; Zhang, Yandong1,7

2020-08-24

10.1111/cas.14601

CANCER SCIENCE   影响因子和分区

1347-9032

1349-7006

Ras has been found to be mutated in 30% of non-small cell lung cancers, and its mutation has been regarded as a causal factor underlying tumorigenesis. However, no successful medicine has been developed so far to inhibit Ras for lung cancer treatment. We have previously identified DHX33 as a Ras downstream effector, promoting cell cycle progression and cell growth. In this study, with the K-Ras (G12D);DHX33 (lox/lox) mouse model, we discovered that genetic ablation of DHX33 inhibited tumor development. We further found that ablation of DHX33 altered the expression of nearly 2000 genes which are critical in cancer development such as cell cycle, apoptosis, glycolysis, Wnt signaling, and cell migration. Our study for the first time demonstrates the pivotal role of the DHX33 in Ras-driven lung cancer development in vivo and highlights that pharmacological targeting DHX33 can be a feasible option in treating Ras-mutant lung cancers.

DHX33 lung cancer oncogene Ras RNA helicase

SCI

英语

第一 ; 通讯

Shenzhen Science and Technology Innovation Commission[CKCY20170721164627271]

Oncology

Oncology

WOS:000562037800001

WILEY

CLINICAL MEDICINE

Web of Science

1.Southern Univ Sci & Technol, Dept Biol, Shenzhen, Peoples R China
2.Univ Macau, Fac Hlth Sci, Macau, Peoples R China
3.State Key Lab Cell Biol, Shanghai, Peoples R China
4.CAS Ctr Excellence Mol Cell Sci, Shanghai, Peoples R China
5.Chinese Acad Sci, Innovat Ctr Cell Signaling Network, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai, Peoples R China
6.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
7.KeYe Life Technol Co Ltd, Room 203,Bldg 1,Block B, Shenzhen, Guangdong, Peoples R China

Wang, Xingshun,Feng, Weimin,Peng, Cheng,et al. Targeting RNA helicase DHX33 blocks Ras-driven lung tumorigenesis in vivo[J]. CANCER SCIENCE,2020,111(10):3564-3575.

Wang, Xingshun.,Feng, Weimin.,Peng, Cheng.,Chen, Shiyun.,Ji, Hongbin.,...&Zhang, Yandong.(2020).Targeting RNA helicase DHX33 blocks Ras-driven lung tumorigenesis in vivo.CANCER SCIENCE,111(10),3564-3575.

Wang, Xingshun,et al."Targeting RNA helicase DHX33 blocks Ras-driven lung tumorigenesis in vivo".CANCER SCIENCE 111.10(2020):3564-3575.