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Knockdown of RhoQ, a member of Rho GTPase, accelerates TGF-β-induced EMT in human lung adenocarcinoma

Kotone Satoh1, Satoshi Sakai2, Makoto Nishizuka1

  • 1Department of Applied Biology and Food Sciences, Faculty of Agriculture and Life Science, Hirosaki University, 3 Bunkyo-cho, Hirosaki, Aomori, 036-8561, Japan.

Biochemistry and Biophysics Reports
|September 19, 2022
PubMed

Insights

RhoQ suppresses epithelial-mesenchymal transition (EMT) and invasion in lung adenocarcinoma (LUAD). Low RhoQ levels correlate with poor patient survival, highlighting its potential as a therapeutic target.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Biology

Background:

  • Lung adenocarcinoma (LUAD) is a leading cause of cancer mortality.
  • RhoQ, a Rho family GTPase, has known roles in cell motility and metabolism, but its function in LUAD is unknown.

Purpose of the Study:

  • To investigate the role of RhoQ in the progression of lung adenocarcinoma.
  • To determine the relationship between RhoQ expression and patient prognosis.

Main Methods:

  • RhoQ was suppressed using siRNA in LUAD cell lines (A549, PC-9).
  • Epithelial-mesenchymal transition (EMT) markers, cell invasion, and TGF/Smad signaling pathway components were analyzed via Western blot and transwell assays.
  • Kaplan-Meier plotter was used to assess the correlation between RhoQ expression and LUAD patient survival.

Main Results:

  • RhoQ suppression enhanced TGF-β-induced EMT and invasion in LUAD cells.
  • Knockdown of RhoQ led to increased Smad3 phosphorylation and Snail expression, implicating RhoQ in TGF/Smad signaling.
  • Low RhoQ expression was significantly associated with poorer overall survival in LUAD patients.

Conclusions:

  • RhoQ acts as a negative regulator of TGF-β-mediated EMT and invasion in lung adenocarcinoma.
  • RhoQ may serve as a prognostic biomarker and a potential therapeutic target for LUAD.
Keywords:
Cdc42, Cell division cycle 42DMEM, Dulbecco's Modified Eagle's MediumEMTEMT, Epithelial-to-Mesenchymal TransitionERK, Extracellular signal-related kinaseFBS, Fetal Bovine SerumLUAD, Lung adenocarcinomaLung adenocarcinomaMEK, Mitogen-activated protein kinase kinaseNSCLC, Non-Small-Cell Lung CancerRhoQSDS, Sodium Dodecyl SulfateTGF-βTGF-β, Transforming Growth Factor-betaTRITC, tetramethylrhodamine-isothiocyanateqPCR, Quantitative Polymerase Chain ReactionrRNA, Ribosomal ribonucleic acidsiRNA, Small Interfering RNA

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