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

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.

SUBMITTER: Han KH

PROVIDER: S-EPMC6862215 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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

Han Kyung Ho KH Kwak Minseok M Lee Tae Hyeong TH Park Min-Soo MS Jeong In-Ho IH Kim Min Ji MJ Jin Jun-O JO Lee Peter Chang-Whan PC

International journal of molecular sciences 20191024 21

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 inhibitor ...[more]

PMID: 31653087

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