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Research on the mechanism of GRIM-19 affecting lung adenocarcinoma through regulating MDM2 and EMT pathways

Pengfei Guo1, Song Zhao1, Xiaoli Han1

  • 1Department of Thoracic Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China.

Cytotechnology
|July 2, 2025
PubMed

Insights

Growth arrest and DNA-damage-inducible protein 19 (GRIM-19) inhibits lung adenocarcinoma progression by suppressing MDM2 expression. This study reveals GRIM-19

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Lung adenocarcinoma is characterized by decreased GRIM-19 and increased MDM2 expression.
  • The specific relationship between GRIM-19 and MDM2 in lung adenocarcinoma remains unelucidated.

Purpose of the Study:

  • To investigate the correlation between GRIM-19 and MDM2 in lung adenocarcinoma.
  • To explore the functional role of GRIM-19 in lung adenocarcinoma progression and metastasis.

Main Methods:

  • Analysis of GRIM-19 and MDM2 mRNA expression in lung adenocarcinoma tissues.
  • Pearson correlation analysis to determine the relationship between GRIM-19 and MDM2.
  • Experimental validation of GRIM-19's effect on MDM2 protein levels and lung adenocarcinoma cell behavior (proliferation, invasion, migration, apoptosis) in vitro and in vivo.
  • Assessment of epithelial-mesenchymal transition (EMT) markers following GRIM-19 overexpression.

Main Results:

  • GRIM-19 mRNA expression was significantly reduced, while MDM2 mRNA expression was increased in lung adenocarcinoma.
  • A strong negative correlation (r = -0.970, p < 0.001) was observed between GRIM-19 and MDM2 mRNA levels.
  • Overexpression of GRIM-19 decreased MDM2 protein levels, inhibited cell proliferation, invasion, and migration, promoted apoptosis, and suppressed tumor growth in nude mice.
  • GRIM-19 modulated the expression of EMT markers (Snail, N-Cadherin, E-Cadherin, Vimentin), suggesting regulation of the EMT pathway.

Conclusions:

  • GRIM-19 plays a crucial role in inhibiting lung adenocarcinoma development and progression.
  • GRIM-19 may exert its tumor-suppressive effects by downregulating MDM2 expression and inhibiting the EMT pathway.
Keywords:
Adenocarcinoma of the lungEMTGRIM-19MDM2

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