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E3 ligase SOCS3 regulates NOD2 expression by ubiquitin proteasome system in lung cancer progression

In-Ho Jeong1, Jae Kwang Yun2, Jun-O Jin3

  • 1Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea.

Cellular Oncology (Dordrecht, Netherlands)
|November 1, 2023
PubMed
Abstract

Insights

This study identifies Suppressor of Cytokine Signaling 3 (SOCS3) as a key driver in lung cancer progression. Targeting SOCS3 and its interaction with Nucleotide-binding Oligomerization Domain 2 (NOD2) offers a promising new strategy for lung cancer diagnosis and therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Lung cancer remains a leading cause of cancer mortality with limited effective treatments.
  • There is an urgent need for novel diagnostic and therapeutic targets to improve patient outcomes.

Purpose of the Study:

  • To investigate the roles of Suppressor of Cytokine Signaling 3 (SOCS3) and Nucleotide-binding Oligomerization Domain 2 (NOD2) in lung cancer.
  • To explore SOCS3 and NOD2 as potential theranostic targets for lung cancer.

Main Methods:

  • Assessed SOCS3 expression in lung cancer tissues.
  • Utilized gene knockdown and overexpression in lung cancer cell lines to evaluate proliferation, migration, and invasion.
  • Investigated the interaction between SOCS3 and NOD2, including ubiquitination.
  • Examined the effect of NOD2 overexpression on lung cancer cell tumorigenicity via the MAPK pathway.

Main Results:

  • SOCS3 expression was elevated in lung tumor tissues compared to normal tissues.
  • Overexpression of SOCS3 enhanced lung cancer cell proliferation, migration, and invasion.
  • SOCS3 directly ubiquitinates NOD2, and higher SOCS3 levels correlated with lower NOD2 expression in tumors.
  • Overexpression of NOD2 suppressed lung cancer cell tumorigenicity, mediated by the MAPK pathway.

Conclusions:

  • SOCS3 plays a significant role in lung tumorigenesis.
  • SOCS3 and NOD2 represent novel therapeutic and diagnostic targets for lung cancer.
  • This research highlights potential new avenues for lung cancer treatment and diagnosis.
Keywords:
Lung cancerMAPKNOD2SOCS3UPS

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