2023 World Conference on Lung Cancer (Posters)-EP03.02. miR-4487 Enhances Gefitinib-Mediated Ubiquitination and Autophagic Degradation of EGFR in NSCLC cells by targeting USP37

EP03.02. miR-4487 Enhances Gefitinib-Mediated Ubiquitination and Autophagic Degradation of EGFR in NSCLC cells by targeting USP37 - PDF(Slides)

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A study conducted by researchers from Wonkwang University in South Korea has identified a potential target for treating non-small cell lung cancer (NSCLC) and overcoming resistance to the anti-cancer drug gefitinib. In NSCLC, epidermal growth factor receptor (EGFR) mutations are commonly found, and EGFR tyrosine kinase inhibitors (TKIs) like gefitinib are the first-line treatment. However, the mechanisms underlying TKI-mediated EGFR degradation are not well understood.<br /><br />The researchers found that gefitinib induces EGFR degradation in NSCLC cells through autophagy, a process that involves the targeted degradation of cellular components. They also observed that gefitinib reduces the expression of a protein called USP37, which is involved in EGFR degradation. Further investigation revealed an increase in the level of a microRNA called miR-4487 in response to gefitinib treatment. MiR-4487 was found to directly target USP37, leading to enhanced ubiquitination, autophagy, and degradation of EGFR. Depletion of USP37 and overexpression of miR-4487 increased the effectiveness of gefitinib-induced cell death in NSCLC cells.<br /><br />The study suggests that miR-4487 could be a potential therapeutic target for NSCLC and that miR-4487/USP37-regulated EGFR degradation plays a role in developing resistance to gefitinib. Understanding the mechanisms involved in TKI-mediated EGFR degradation could aid in the development of strategies to overcome resistance to EGFR TKIs and improve the effectiveness of NSCLC treatments.<br /><br />The findings of this study suggest a potential new avenue for targeted therapy in NSCLC and provide insights into the underlying mechanisms of EGFR degradation in response to gefitinib. However, further research is needed to validate these findings and explore the potential clinical applications of targeting miR-4487/USP37 in NSCLC treatment.

Asset Subtitle

Sei-hoon Yang

Meta Tag

Speaker Sei-hoon Yang

Topic Tumor Biology: Translational Biology - Drug Resistance

Keywords

Wonkwang University

NSCLC

gefitinib

EGFR mutations

autophagy

USP37

miR-4487

ubiquitination

cell death

targeted therapy