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(Abstract)

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This presentation focuses on the role of miR-4487 in enhancing the effectiveness of gefitinib, a tyrosine kinase inhibitor, in treating non-small cell lung cancer (NSCLC). EGFR mutations are commonly found in NSCLC cells, and EGFR-TKIs are widely used as a first-line treatment for this type of cancer. However, the exact mechanisms by which these inhibitors degrade EGFR are still unknown. <br /><br />The researchers examined the effects of miR-4487 and the ubiquitin-specific peptidase 37 (USP37) in mediating EGFR degradation in NSCLC cells treated with gefitinib. They found that gefitinib can degrade EGFR under normal culture conditions, and this degradation is dependent on autophagic flux and the mutation variants of EGFR. Gefitinib also reduced the expression levels of USP37, which mediates EGFR degradation similar to gefitinib. <br /><br />Furthermore, the researchers observed that gefitinib treatment resulted in an increase in the levels of miR-4487, and this miRNA directly targets USP37, enhancing ubiquitination, autophagy, and subsequent EGFR degradation. Depleting USP37 and overexpressing miR-4487 led to an increase in gefitinib-mediated apoptotic cell death. <br /><br />These findings suggest that miR-4487 could be a potential target for treating NSCLC, and its regulation of EGFR degradation through the targeting of USP37 is crucial in the development of gefitinib resistance. This research provides insights into the molecular mechanisms underlying gefitinib-mediated EGFR degradation and highlights the potential of miR-4487 as a therapeutic target for NSCLC.

Asset Subtitle

Sei-hoon Yang

Meta Tag

Speaker Sei-hoon Yang

Topic Tumor Biology: Translational Biology - Drug Resistance

Keywords

miR-4487

gefitinib

NSCLC

EGFR mutations

USP37

autophagy

apoptotic cell death

gefitinib resistance

molecular mechanisms

therapeutic target