Abstract
CUE domain-containing 2 (CUEDC2) is a multi-functional protein, which regulates cell cycle, growth factor signaling and inflammation. We found that CUEDC2 was low in lung adenocarcinoma cell lines and lung adenocarcinoma tissues at both mRNA and protein levels. Low levels of CUEDC2 were correlated with a shorter survival time in patients with lung adenocarcinoma (p = 0.004). CUEDC2 expression was correlated with tumor T classification (P = 0.001) at clinical stage (P = 0.001) and tumor size (P = 0.033). Multivariate analysis suggested that CUEDC2 expression is an independent prognostic indicator for patients with lung adenocarcinoma. Ectopic expression of CUEDC2 decreased cell proliferation in vitro and inhibited tumor growth in nude mice in vivo. Knockdown of endogenous CUEDC2 by short hairpin RNAs (shRNAs) increased tumor growth. Inhibition of proliferation by CUEDC2 was associated with inactivation of the PI3K/Akt pathway, induction of p21 and down-regulation of cyclin D1. Our results suggest that decreased expression of CUEDC2 contributes to tumor growth in lung adenocarcinoma, leading to a poor clinical outcome.
Highlights
IntroductionLung cancer is one of the most commonly diagnosed cancer [1,2,3], Identification and characterization of oncogenes and tumor suppressor genes involved in lung carcinogenesis may reveal new therapeutic targets and prognostic biomarkers
Lung cancer is one of the most commonly diagnosed cancer [1,2,3], Identification and characterization of oncogenes and tumor suppressor genes involved in lung carcinogenesis may reveal new therapeutic targets and prognostic biomarkers.CUE domain-containing 2 (CUEDC2) is a multifunctional protein that is involved in cell cycle, growth factor signaling and inflammation [4]
In contrast to previous reports that CUEDC2 was highly expressed in many types of cancers, our study suggested that CUEDC2 was markedly down-regulated in lung adenocarcinoma cells and surgical specimens of lung adenocarcinoma
Summary
Lung cancer is one of the most commonly diagnosed cancer [1,2,3], Identification and characterization of oncogenes and tumor suppressor genes involved in lung carcinogenesis may reveal new therapeutic targets and prognostic biomarkers. CUE domain-containing 2 (CUEDC2) is a multifunctional protein that is involved in cell cycle, growth factor signaling and inflammation [4]. The CUE domain, a small ubiquitin-binding motif of about 40 amino acids, can recognize both mono- and poly-ubiquitin and facilitates intermolecular mono-ubiquitination [5, 6]. CUEDC2 interacts with progesterone receptor (PR) and promotes progesterone-induced ubiquitination and degradation of receptors [7]. CUEDC2 is involved in carcinogenesis [7,8,9]. CUEDC2 is highly expressed in ovarian, brain, kidney and breast tumors [8, 9]
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