USP14 Inhibition Regulates Tumorigenesis by Inducing Autophagy in Lung Cancer In Vitro

International Journal of Molecular Sciences

In-ho Jeong¹  MinJi Kim¹  KyungHo Han¹  TaeHyeong Lee¹  PeterChang-Whan Lee¹  Min-soo Park¹  Minseok Kwak²  Jun-O Jin³ 

[1] Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea;Department of Chemistry, Pukyong National University, Busan 48513, Korea;Department of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, Korea;

关键词: ubiquitin-specific protease 14;    deubiquitinating enzyme;    lung cancer;    autophagy;   

DOI  :  10.3390/ijms20215300

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown