Open AccessTargeting RNA helicase DHX33 blocks Ras‐driven lung tumorigenesis in vivo
Author(s) -
Wang Xingshun,
Feng Weimin,
Peng Cheng,
Chen Shiyun,
Ji Hongbin,
Zhong Hanbing,
Ge Wei,
Zhang Yandong
Publication year - 2020
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14601
Subject(s) - carcinogenesis , wnt signaling pathway , cancer research , biology , cell cycle , cell growth , lung cancer , in vivo , rna helicase a , effector , cancer , microbiology and biotechnology , signal transduction , gene , medicine , helicase , rna , pathology , genetics
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.