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

First Author  Wang X Year  2020
Journal  Cancer Sci Volume  111
Issue  10 Pages  3564-3575
PubMed ID  32767810 Mgi Jnum  J:299900
Mgi Id  MGI:6490797 Doi  10.1111/cas.14601
Citation  Wang X, et al. (2020) Targeting RNA helicase DHX33 blocks Ras-driven lung tumorigenesis in vivo. Cancer Sci 111(10):3564-3575
abstractText  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.
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