Expression of HNF4G and its potential functions in lung cancer
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Jingyu Wang1, Jun Zhang2, Longsheng Xu3, Ying Zheng3, Danyan Ling4 and Zhiping Yang5
1Department of Pathology, The First Affiliated Hospital of Jiaxing University, Jiaxing, China
2Department of Chest Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China
3Department of Central laboratory, The First Affiliated Hospital of Jiaxing University, Jiaxing, China
4Department of Cell Division, Shanghai Emay Biotechnologies Co., Ltd, Shanghai, China
5Department of Oncology (04-F-14), The First Affiliated Hospital of Jiaxing University, Jiaxing, China
Zhiping Yang, email: [email protected]
Keywords: HNF4G; AKT; lung cancer; proliferation; apoptosis
Received: July 20, 2017 Accepted: October 30, 2017 Epub: December 04, 2017 Published: April 06, 2018
The hepatocyte nuclear factor 4 gamma (HNF4G), a member of orphan nuclear receptors, is up-regulated and functions as an oncoprotein in bladder cancer. In the present study, we observed that HNF4G expression was elevated in lung cancer tissues as compared to adjacent normal lung tissues. The expression of HNF4G protein was correlated with the tumor size and the prognosis of patients. Transfection with a small interference RNA (siRNA) targeting HNF4G in two lung cancer cell lines (H358 and H292 cells) significantly inhibited cell proliferation via arresting cells at G1 phase and inducing cell apoptosis. In addition, HNF4G siRNA reduced cell proliferation in a xenograft tumor-bearing model. Moreover, A549 cells, which had relative lower level of HNF4G, were ectopic expressed with HNF4G and treated with an AKT inhibitor (MK-2206). MK-2206 exposure not only attenuated the promoting effects of HNF4G overexpression on cell proliferation and cell cycle progression, but also suppressed the inhibitory effects of HNF4G overexpression on cell apoptosis. These data suggested that AKT signaling pathway was a potential upstream mediator of HNF4G. Collectively, our data indicate that HNF4G exerts as an oncogenic role in lung cancer by promoting cell proliferation and that HNF4G expression is a potential prognosis factor for lung cancer.
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