Research Papers:

CUEDC2 down-regulation is associated with tumor growth and poor prognosis in lung adenocarcinoma

Longhua Sun, Lihong Bai, Gengpeng Lin, Rang Wang, Yangli Liu, Jinghuang Cai, Yubiao Guo, Zhiwen Zhu _ and Canmao Xie

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Oncotarget. 2015; 6:20685-20696. https://doi.org/10.18632/oncotarget.3930

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Longhua Sun1,3,*, Lihong Bai1,*, Gengpeng Lin1,*, Ran Wang2, Yangli Liu1, Jinghuang Cai1, Yubiao Guo1, Zhiwen Zhu1, Canmao Xie1

1Department of Respiratory, The First Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China

2Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China

3Respiratory Department, Nanchang Hospital of Integrative Traditional Chinese and Western Medicine, Jiangxi University of Traditional Chinese Medicine Nanchang, Jiangxi, People’s Republic of China

*These authors have contributed equally to this work

Correspondence to:

Canmao Xie, e-mail: [email protected]

Zhiwen Zhu, e-mail: [email protected]

Keywords: CUEDC2, lung adenocarcinoma, clinical outcome, proliferation, Akt

Received: September 03, 2014     Accepted: April 30, 2015     Published: May 13, 2015


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.

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