Inflammation suppresses DLG2 expression decreasing inflammasome formation.

Area of Science:

• Molecular biology
• Immunology
• Oncology

Background:

• Loss of DLG2 expression is linked to increased tumor cell proliferation and poor survival in various cancers.
• Previous research suggests DLG2 influences the cell cycle and proliferation, and may be involved in the NLRP3 inflammasome pathway.
• The precise immune function of DLG2 remains largely unelucidated.

Purpose of the Study:

• To investigate the role of DLG2 in inflammatory colon diseases and colon cancer.
• To determine the impact of DLG2 on inflammasome induction and activation.
• To explore the relationship between DLG2 expression and cellular processes like proliferation and signaling.

Main Methods:

• DLG2 expression levels were analyzed in publicly available datasets of inflammation, colon cancer, and mouse models.
• Overexpression and silencing of DLG2 were performed in colon cancer cells to assess its effect on inflammasome activation and cytokine release.
• Cell and animal models were utilized to study the dynamic changes in DLG2 expression during inflammation.

Main Results:

• DLG2 expression was found to be repressed in inflammatory colon diseases (IBD, Ulcerative Colitis) and colorectal cancer tissues compared to healthy controls.
• Inflammatory stimuli induced a biphasic alteration in DLG2 expression (initial increase followed by decrease) in cell and animal models.
• DLG2 overexpression significantly increased the expression of IL1B, IκBζ, and BAX, key components of inflammasome formation.
• DLG2 silencing in THP1 cells led to increased IL-6 release, promoting STAT3 phosphorylation and proliferation in bystander COLO205 cells.
• Restoration of DLG2 in the colon reduced AKT and S6 signaling.

Conclusions:

• DLG2 expression is significantly altered in response to gut inflammation and colon cancer.
• These alterations in DLG2 expression affect the colon's ability to form inflammasomes.
• DLG2 plays a crucial role in regulating inflammatory responses and cellular processes relevant to colon cancer development.