Identification of an E3 ligase-encoding gene RFWD3 in non-small cell lung cancer

Published on Jun 8, 2020in Frontiers of Medicine in China
· DOI :10.1007/S11684-019-0708-6
Yan-Fei Zhang3
Estimated H-index: 3
(CAS: Chinese Academy of Sciences),
Xinchun Zhao1
Estimated H-index: 1
(USTC: University of Science and Technology of China)
+ 2 AuthorsGuang-Biao Zhou34
Estimated H-index: 34
(CAS: Chinese Academy of Sciences)
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, RFWD3 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 Z-scores. Knockdown of RFWD3 suppressed colony forming activity of NSCLC cells.We further evaluated the significance of RFWD3 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, RFWD3 expression was significantly higher in smokers than in non-smokers. These results show for the first time that RFWD3 is required for NSCLC cell proliferation and may have an important role in lung carcinogenesis.
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