YBX1 regulates tumor growth via CDC25a pathway in human lung adenocarcinoma
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Shilei Zhao1,3,*, Yan Wang2,*, Tao Guo1,3,*, Wendan Yu1, Jinxiu Li3, Zhipeng Tang1, Zhenlong Yu1, Lei Zhao1,3, Yixiang Zhang1,3, Ziyi Wang1,3, Peng Wang1,3, Yechi Li1,3, Fengzhou Li1, Zhe Sun1,3, Yang Xuan1, Ranran Tang1, Wu-guo Deng4,5, Wei Guo1, Chundong Gu1,3
1The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China
2Department of Respiratory Medicine, The People’s Hospital of Liaoning Province, Shenyang, China
3Lung Cancer Diagnosis and Treatment Center of Dalian, Dalian, China
4Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
5State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, China
*These authors have contributed equally to this work
Chundong Gu, email: [email protected]
Wei Guo, email: [email protected]
Keywords: YBX1, CDC25a, cell cycle regulation, prognosis, lung adenocarcinoma
Received: November 07, 2015 Accepted: May 28, 2016 Published: June 15, 2016
Y-box binding protein 1 (YBX1) is involved in the multi-tumor occurrence and development. However, the regulation of YBX1 in lung tumorigenesis and the underlying mechanisms, especially its relationship with CDC25a, was remains unclear. In this study, we analyzed the expression and clinical significance of YBX1 and CDC25a in lung adenocarcinoma and identified their roles in the regulation of lung cancer growth. The retrospective analysis of 116 patients with lung adenocarcinoma indicated that YBX1 was positively correlated with CDC25a expression. The Cox-regression analysis showed only high-ranking TNM stage and low CDC25a expression were an independent risk factor of prognosis in enrolled patients. High expression of YBX1 or CDC25a protein was also observed in lung adenocarcinoma cells compared with HLF cells. ChIP assay demonstrated the binding of endogenous YBX1 to the CDC25a promoter region. Overexpression of exogenous YBX1 up-regulated the expression of the CDC25a promoter-driven luciferase. By contrast, inhibition of YBX1 by siRNA markedly decreased the capability of YBX1 binding to CDC25a promoter in A549 and H322 cells. Inhibition of YBX1 expression also blocked cell cycle progression, suppressed cell proliferation and induced apoptosis via the CDC25a pathway in vitro. Moreover, inhibition of YBX1 by siRNA suppressed tumorigenesis in a xenograft mouse model and down-regulated the expression of YBX1, CDC25a, Ki67 and cleaved caspase 3 in the tumor tissues of mice. Collectively, these results demonstrate inhibition of YBX1 suppressed lung cancer growth partly via the CDC25a pathway and high expression of YBX1/CDC25a predicts poor prognosis in human lung adenocarcinoma.
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