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2020, Volume 14, Issue 3

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Frontiers of Medicine >> 2020, Volume 14, Issue 3 doi: 10.1007/s11684-019-0708-6

Identification of an E3 ligase-encoding gene

. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.. State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.. University of Chinese Academy of Sciences, Beijing 100049, China.. School of Life Sciences, University of Science and Technology of China, Hefei 230026, China.. Department of Thoracic Surgery, the Third Affiliated Hospital of Kunming Medical University, Kunming 650106, China

Accepted: 2019-10-09 Available online: 2019-10-09
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Abstract

In order to unveil ubiquitin pathway genes (UPGs) that are essential for non-small cell lung cancer (NSCLC) cell proliferation, we recently conducted a siRNA screening experiment to knockdown the expression of 696 UPGs found in the human genome in A549 and H1975 NSCLC cells. We found that silencing of one of the candidates, that encodes an E3 ubiquitin ligase essential for the repair of DNA interstrand cross-links in response to DNA damage, led to dramatic inhibition of NSCLC cell proliferation with significant -scores. Knockdown of suppressed colony forming activity of NSCLC cells. We further evaluated the significance of in NSCLCs and found that this gene was more elevated in tumor samples than in paired normal lung tissues and was inversely associated with the clinical outcome of patients with NSCLC. Moreover, expression was significantly higher in smokers than in non-smokers. These results show for the first time that is required for NSCLC cell proliferation and may have an important role in lung carcinogenesis.

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