BPTF promotes tumor growth and predicts poor prognosis in lung adenocarcinomas
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Meng Dai1,*, Jian-Jun Lu3,*, Wei Guo1, Wendan Yu1, Qimin Wang4, Ranran Tang1, Zhipeng Tang1, Yao Xiao1, Zhenglin Li1, Wei Sun1, Xiuna Sun1, Yu Qin1, Wenlin Huang2,5, Wu-guo Deng2,5, Taihua Wu1
1The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Central Hospital, Dalian Medical University, Dalian, China
2Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
3Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen University Cancer Center, Guangzhou, China
4The Second Affiliated Hospital, Dalian Medical University, Dalian, 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
Wuguo Deng, e-mail: [email protected]
Taihua Wu, e-mail: [email protected]
Keywords: BPTF, lung cancer, tumor growth, prognosis
Received: March 12, 2015 Accepted: September 11, 2015 Published: September 21, 2015
BPTF, a subunit of NURF, is well known to be involved in the development of eukaryotic cell, but little is known about its roles in cancers, especially in non-small-cell lung cancer (NSCLC). Here we showed that BPTF was specifically overexpressed in NSCLC cell lines and lung adenocarcinoma tissues. Knockdown of BPTF by siRNA significantly inhibited cell proliferation, induced cell apoptosis and arrested cell cycle progress from G1 to S phase. We also found that BPTF knockdown downregulated the expression of the phosphorylated Erk1/2, PI3K and Akt proteins and induced the cleavage of caspase-8, caspase-7 and PARP proteins, thereby inhibiting the MAPK and PI3K/AKT signaling and activating apoptotic pathway. BPTF knockdown by siRNA also upregulated the cell cycle inhibitors such as p21 and p18 but inhibited the expression of cyclin D, phospho-Rb and phospho-cdc2 in lung cancer cells. Moreover, BPTF knockdown by its specific shRNA inhibited lung cancer growth in vivo in the xenografts of A549 cells accompanied by the suppression of VEGF, p-Erk and p-Akt expression. Immunohistochemical assay for tumor tissue microarrays of lung tumor tissues showed that BPTF overexpression predicted a poor prognosis in the patients with lung adenocarcinomas. Therefore, our data indicate that BPTF plays an essential role in cell growth and survival by targeting multiply signaling pathways in human lung cancers.
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