IGF2BP3 Enhances GSDMD Stability and Blocks JNK Signaling Activation to Promote Eyelid Basal Cell Carcinoma...

Area of Science:

• Oncology
• Molecular Biology
• Cellular Signaling

Background:

• Eyelid basal cell carcinoma (BCC) is a common skin cancer.
• The molecular mechanisms underlying BCC development and progression require further elucidation.
• Understanding key protein interactions and signaling pathways is crucial for targeted therapies.

Purpose of the Study:

• To investigate the role of the Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and Gasdermin D (GSDMD) axis in eyelid BCC.
• To elucidate the mechanism by which IGF2BP3/GSDMD modulates JNK signaling activation in eyelid BCC.
• To explore the potential of targeting this axis for BCC treatment.

Main Methods:

• Utilized human BCC cell lines (TE354.T) transfected with vectors targeting IGF2BP3 and GSDMD.
• Assessed changes in cell proliferation, migration, invasion, pyroptosis, and inflammatory response post-transfection.
• Analyzed protein expression, co-localization, m6A modification of GSDMD mRNA, and tumor growth in nude mice.

Main Results:

• IGF2BP3 stabilized GSDMD mRNA, reducing BCC proliferation, invasion, and migration while increasing pyroptosis.
• The IGF2BP3/GSDMD axis was found to block JNK pathway activation in BCC.
• IGF2BP3 inhibited tumor formation by enhancing GSDMD stability.

Conclusions:

• IGF2BP3 enhances GSDMD stability, promoting eyelid BCC pyroptosis.
• The IGF2BP3/GSDMD axis blocks JNK signaling activation.
• This interaction occurs in an m6A-dependent manner, offering a potential therapeutic target for BCC.