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

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.

Downregulation of CUEDC2 prevents doxorubicin‑induced cardiotoxicity in H9c2 cells

“…The results of the present study are supported by results of a previous study where overexpression of CUEDC2 was considered a predictor of poor prognosis of ovarian serous carcinoma ( 42 ). However, a recent study reported that CUEDC2 knockdown could increase tumor growth in lung adenocarcinoma ( 43 ). It has therefore been suggested that the function of CUEDC2 may be dependent on cell type.…”

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“…Western blotting was performed as previously described [22, 23]. Briefly, cells were lysed in radio-immunoprecipitation buffer, and clarified lysates were resolved by SDS-PAGE and transferred onto polyvinylidene fluoride membranes (Millipore, Bedford, MA).…”

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“…Western blotting was performed as previously described. 30 , 31 In brief, tissues and cells were lysed in RIPA buffer (Beyotime, Haimen, People’s Republic of China), and after centrifugation at 13,000 g for 15 min, the concentration of protein in the supernatant was measured using BCA kit (Pierce, Waltham, MA, USA). Approximately 50 μg protein was resolved by 10% SDS-PAGE and transferred onto PVDF membranes (EMD Millipore, Billerica, MA, USA).…”