Abstract
The molecular pathogenesis of human lung cancer has not been completely clarified. Here, we reported that UBE2L3, a member of the ubiquitin-conjugating enzymes (E2s), were overexpressed in non-small-cell lung cancer (NSCLC) tissues compared with the non-tumor tissues. High expression of UBE2L3 was correlated with advanced tumor stage and adverse outcomes. Knockdown of UBE2L3 inhibited NSCLC cell growth while ectopic expression of UBE2L3 promoted NSCLC cell growth in a cell cycle dependent manner. The results of subcutaneous tumor xenograft studies revealed that knockdown of UBE2L3 attenuated the in vivo tumor growth. Mechanistically, we observed that UBE2L3 could interact with F-box protein Skp2, a member of the SCF (Skp2) ubiquitin ligase complex, and thus promoted the ubiquitination and proteasomal degradation of p27kip1. Furthermore, NSCLC cases with high level of UBE2L3 and low level of p27kip1 had worst prognosis, suggesting that combination of UBE2L3 and p27kip1 is a more powerful prognostic marker for NSCLC patients. Taken together, the current study presented a novel marker for predicting prognosis and a potential therapeutic target for NSCLC patients.
Highlights
Lung cancer remains the leading cause of cancer death worldwide with a 5-year survival rate less than 15 % [1, 2]
ubiquitin conjugating enzyme E2 L3 (UBE2L3) is overexpressed in non-small-cell lung cancer (NSCLC) tissues and correlates with poor prognosis of NSCLC patients
In NSCLC, overexpression of UBE2C in tumor tissues was correlated with advanced tumor stage and apoptosis dependent cell proliferation [19]
Summary
Lung cancer remains the leading cause of cancer death worldwide with a 5-year survival rate less than 15 % [1, 2]. Emerging evidences have indicated that post-translational modifications, including ubiquitination, phosphorylation, and methylation of tumor progression related proteins were involved in the carcinogenesis of NSCLC, implicating a potential to develop novel prognostic biomarkers and therapeutic strategies for this deadly disease, which still need further investigations [3,4,5]. The clinical expression or biological significance of ubiquitin conjugating enzyme E2 L3 (UBE2L3) was rarely reported in human malignancies. A recent literature revealed that UBE2L3 could regulate the stability of tumor suppressor p53-binding protein 1 (53BP1), which was an important anticancer target of human tumors [14]. We investigated the clinical significance and biological function of UBE2L3 in NSCLC
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