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

Xingshun Wang1,2, Weimin Feng1, Cheng Peng1,2

  • 1Department of Biology, Southern University of Science and Technology, Shenzhen, China.

Cancer Science
|August 9, 2020
PubMed

Insights

Targeting DHX33, a Ras downstream effector, inhibits tumor development in Ras-mutant lung cancer. This study reveals DHX33

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Ras mutations drive 30% of non-small cell lung cancers (NSCLC).
  • No effective drugs currently target Ras for NSCLC treatment.
  • DHX33 was previously identified as a Ras downstream effector promoting cell growth.

Purpose of the Study:

  • To investigate the role of DHX33 in Ras-driven lung cancer development in vivo.
  • To explore DHX33 as a potential therapeutic target for Ras-mutant NSCLC.

Main Methods:

  • Utilized a K-Ras (G12D);DHX33 (lox/lox) mouse model.
  • Performed genetic ablation of DHX33.
  • Analyzed gene expression changes following DHX33 ablation.

Main Results:

  • Genetic ablation of DHX33 significantly inhibited tumor development.
  • DHX33 ablation altered the expression of approximately 2000 genes.
  • Affected genes are critical for cell cycle, apoptosis, glycolysis, Wnt signaling, and cell migration.

Conclusions:

  • DHX33 plays a pivotal role in Ras-driven lung cancer development.
  • Pharmacological targeting of DHX33 presents a feasible strategy for treating Ras-mutant lung cancers.