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USP14 Inhibition Regulates Tumorigenesis by Inducing Autophagy in Lung Cancer In Vitro
Kyung Ho Han1, Minseok Kwak2, Tae Hyeong Lee3
1Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea. Kyungho1.han@gmail.com.
Abstract:
The ubiquitin-proteasome system is an essential regulator of several cellular pathways involving oncogenes. Deubiquitination negatively regulates target proteins or substrates linked to both hereditary and sporadic forms of cancer. The deubiquitinating enzyme ubiquitin-specific protease 14 (USP14) is associated with proteasomes where it trims the ubiquitin chain on the substrate. Here, we found that USP14 is highly expressed in patients with lung cancer. We also demonstrated that USP14 inhibitors (IU1-47 and siRNA-USP14) significantly decreased cell proliferation, migration, and invasion in lung cancer. Remarkably, we found that USP14 negatively regulates lung tumorigenesis not only through apoptosis but also through the autophagy pathway. Our findings suggest that USP14 plays a crucial role in lung tumorigenesis and that USP14 inhibitors are potent drugs in lung cancer treatment.
Insights
Ubiquitin-specific protease 14 (USP14) is highly expressed in lung cancer and drives tumor growth. Inhibiting USP14 significantly reduced lung cancer cell proliferation and invasion, suggesting its potential as a therapeutic target.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- The ubiquitin-proteasome system regulates cellular pathways crucial for oncogenesis.
- Deubiquitination, mediated by enzymes like ubiquitin-specific protease 14 (USP14), negatively impacts cancer-associated substrates.
- USP14 is implicated in various cancers, but its specific role in lung tumorigenesis requires further elucidation.
Purpose of the Study:
- To investigate the expression and function of USP14 in lung cancer.
- To evaluate the therapeutic potential of USP14 inhibitors in lung cancer models.
Main Methods:
- Quantitative analysis of USP14 expression in lung cancer patient samples.
- In vitro studies using USP14 inhibitors (IU1-47) and genetic knockdown (siRNA-USP14) to assess effects on lung cancer cell lines.
- Assessment of apoptosis and autophagy pathways in response to USP14 inhibition.
Main Results:
- USP14 was found to be highly expressed in lung cancer patients.
- USP14 inhibition significantly reduced lung cancer cell proliferation, migration, and invasion.
- USP14 was shown to negatively regulate lung tumorigenesis via both apoptosis and autophagy pathways.
Conclusions:
- USP14 plays a critical role in the development and progression of lung cancer.
- USP14 inhibitors demonstrate significant anti-cancer activity and represent promising therapeutic agents for lung cancer treatment.
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